Easy Hacks Guide Targeting Different Biomarkers (BMI, apoB, blood pressure, HbA1c, eGFR, etc)

[LukeMV]

Interesting. Here I was thinking it was the Empagliflozin that was raising my eGFR, when it might have been Rosuvastatin/Ezetimibe

[mccoy]

According to the article, the effect is pretty small. If your kidneys are hyperresponders to this treatment, then you might expect a +4 mL/min/1.73m2, at best.

EDIT: I’ve read more carefully that the output in the forest graph is MD with 95% CI. So, assuming MD = Mean data, we can say that on average a +4 mL/min/1.73m2 is a good response, but as we know, there are data outside the CI of the mean, so hyper responders may exhibit well above +4 mL/min/1.73m2

[Olafurpall]

@RobTuck

The research I have read suggests that cellular damage from long term elevation of blood glucose occurs at levels higher than we see in a normal cycle of pre-diabetics or even some early phase diabetics who have normal insulin sensitivity but reduced insulin output due to (to simplify for this discussion) “fatigued or inflamed” beta cells.

Blood glucose causes damage in the body, including to cells, even at very low levels, so even those with normal blood glucose can benefit from lowering the average glucose. HbA1C is actually a proxy for the damage caused by glucose.

[John_Hemming]

I think the damage to mitochondrial DNA from excessive ROS increases substantially with higher levels of glucose. That does not mean that nothing happens at lower levels, but there is clearly a much higher level of damage with higher levels of glucose. I have not done a literature search on this, but I think it should turn up somethign.

[tj_long]

@Olafurpall

Blood glucose causes damage in the body, including to cells, even at very low levels, so even those with normal blood glucose can benefit from lowering the average glucose. HbA1C is actually a proxy for the damage caused by glucose.

What is the source of this claim?

[Olafurpall]

The damage I’m referring to that occurs even at very low levels is glycation. This article I wrote long ago has lots of references on glycation being involved in age-related damage.

Pyridoxamine prevents complications of aging and diabetes

[RapMet]

all good, but where to get pyridoxamine? Checked all over web and could NOT find one single place to source it from? Or should we wait for when Elon colonizes mars, and he can bring us some LOL

[cl-user]

@RapMet

all good, but where to get pyridoxamine?

FDA Seeks to Ban Pyridoxamine

Relying on the published scientific literature, we at Life Extension are replacing pyridoxamine in all of our products with a double-dose of pyridoxal-5’-phosphate. While the cost to us is very high, we are not about to let the FDA’s insanely prejudiced actions deprive our members of this vital vitamin B6 metabolite.

[Joseph_Lavelle]

@Olafurpall any thoughts on GlyLo?

[RapMet]

@cl-user

FDA Seeks to Ban Pyridoxamine

could our friends in India come to the rescue? LOL

[desertshores]

As I understand it the supplement to take is P-5-P, available from Amazon.

“pyridoxamine can convert to pyridoxal 5’-phosphate (P-5-P) through the action of the enzyme pyridoxamine 5’-phosphate oxidase (PNPOx).”

“The active form of vitamin B6 is pyridoxal 5’-phosphate P-5-P), which is essential for various enzymatic reactions in the body, particularly those involving amino acid metabolism.”

[Olafurpall]

@Joseph_Lavelle

@Olafurpall any thoughts on GlyLo?

Yes, I shared my thoughts on GLYLO earlier this year. See here:

Fixing stiff collagens – damage to the extracellular matrix is the missing hallmark of aging

Yes, slowing it down is the main thing we can do today. I have been trying to slow down AGE formation for 15 years. Regarding Pankaj, I am no fan of his GLYLO product for reasons I have explained elsewhere before. I don’t think the GLYLO product is novel at all and I think the marketing of it is downright misleading. Here are the reasons why I think so. The GLYLO product contains five ingredients; Alpha-lipoic acid, nicotinamide, pyridoxine, thiamine and piperine. Only two of these, namely pyridoxine and thiamine, have some direct antiglycating effects. The others do not. Those two ingredients are not particularly powerful and the doses of them in GLYLO are not particularly high, certainly not more than a whole lot of people have already been getting for many years simply by taking multivitamins or vitamin B complex supplements. GLYLO is claimed to result in weight loss and increase insulin sensitivity. That’s not at all unreasonable. Alpha-lipoic acid has been found to improve insu…

[RapMet]

@desertshores

As I understand it the supplement to take is P-5-P, available from Amazon.

@Olafurpall what do you think of above from @desertshores ? or should i contact my indian supplier and ask if they sell Pyridoxamine?

[Joseph_Lavelle]

Thanks. The paper / article your wrote also mentioned that ALA was complementary to B6 so it made me think of Glylo

[Olafurpall]

@RapMet

all good, but where to get pyridoxamine?

This is the only source I’m aware of. It’s not based in the US: https://www.supersmart.com/en/shop/strengthening-organism/pyridoxamine-supplement-0443

@desertshores

As I understand it the supplement to take is P-5-P, available from Amazon.

“pyridoxamine can convert to pyridoxal 5’-phosphate (P-5-P) through the action of the enzyme pyridoxamine 5’-phosphate oxidase (PNPOx).”

“The active form of vitamin B6 is pyridoxal 5’-phosphate P-5-P), which is essential for various enzymatic reactions in the body, particularly those involving amino acid metabolism.”

That doesn’t mean taking P-5-P is best. There are two reasons for this. Firstly, P-5-P is merely the active form at performing the enzymatic reactions that vitamin B6 is used for in the body. It’s not the active form at inhibiting glycation. It can inhibit glycation somewhat, but not as strongly as pyridoxamine. Secondly, even if P-5-P were more beneficial, it isn’t absorbed intact. P-5-P is dephosphorylated into pyridoxine in the digestive tract so when you ingest it you will absorb pyridoxine. So basically taking P-5-P is an expensive way to get pyridoxine, the latter being the cheapest and most common form of vitamin B6 in supplements.

My recommendation for those that cannot get hold on pyridoxamine, or cannot afford to take it is to simply take pyridoxine. Just be careful with the dose because chronic intake of very high doses (100 mg or more daily) can in some people result in peripheral neuropathy. Pyridoxamine has a lower tendency for this so it’s safer at higher doses. It’s a shame pyridoxamine was banned in the US. Maybe it would have been available cheaply if it hadn’t been banned 15 years ago.

[amuser]

@Olafurpall

Just be careful with the dose because chronic intake of very high doses (100 mg or more daily) can in some people result in peripheral neuropathy.

I developed tingling in both feet around September of 2023. ‘Idiopathic peripheral neuropathy.’ Recently, it has gotten really annoying.

I first ordered Glylo in July '23. I didn’t start it right away, don’t remember when exactly. I take just 1/day. So not a ‘high’ dose. I’m not getting B6 from any other supplement.

Anyway, will stop and see if symptoms improve.

[Neo]

Do you know your blood B6 levels? Might be good to get a time series of that.

[tj_long]

@Olafurpall

That doesn’t mean taking P-5-P is best. There are two reasons for this. Firstly, P-5-P is merely the active form at performing the enzymatic reactions that vitamin B6 is used for in the body. It’s not the active form at inhibiting glycation. It can inhibit glycation somewhat, but not as strongly as pyridoxamine. Secondly, even if P-5-P were more beneficial, it isn’t absorbed intact. P-5-P is dephosphorylated into pyridoxine in the digestive tract so when you ingest it you will absorb pyridoxine. So basically taking P-5-P is an expensive way to get pyridoxine, the latter being the cheapest and most common form of vitamin B6 in supplements.

My recommendation for those that cannot get hold on pyridoxamine, or cannot afford to take it is to simply take pyridoxine. Just be careful with the dose because chronic intake of very high doses (100 mg or more daily) can in some people result in peripheral neuropathy. Pyridoxamine has a lower tendency for this so it’s safer at higher doses. It’s a shame pyridoxamine was banned in the US. Maybe it would have been available cheaply if it hadn’t been banned 15 years ago.

Interesting. Just to clarify, you don’t see pyridoxal 5’-phosphate as being worse than pyridoxine, correct? You’re only recommending it due to the price? I’m asking because I use Thorne Methyl-Guard, which contains pyridoxal phosphate (I only take 1 capsule per day since, to me, 3 capsules contain an absurd amount of B vitamins)

[John_Hemming]

I vote p5p. Pyroxidine self inhibits at high level, but i have not found a reference. 100mg daily is enough to cause this.

[Olafurpall]

@amuser

I developed tingling in both feet around September of 2023. ‘Idiopathic peripheral neuropathy.’ Recently, it has gotten really annoying.

I first ordered Glylo in July '23. I didn’t start it right away, don’t remember when exactly. I take just 1/day. So not a ‘high’ dose. I’m not getting B6 from any other supplement.

Is that 1 pill daily, which would be 50 mg of P-5-P daily? It’s possible that neuropathy is from the P-5-P in GLYLO. While it’s rare, there are reports in the literature of people getting neurotoxicity from doses as low as 50 mg daily, so if I were you, I would takea few months off and see if the neuropathy improves. Note that the neuropathy in response to high doses of vitamin B6 takes a while to develop. It doesn’t occur with short term use but comes gradually with chronic use.

@tj_long

Interesting. Just to clarify, you don’t see pyridoxal 5’-phosphate as being worse than pyridoxine, correct? You’re only recommending it due to the price?

Yes, exactly! It’s no worse than pyridoxine just a lot more expensive. Unfortunately, many supplement vendors sell the much more expensive P-5-P claiming that it’s better than pyridoxine and a lot of people are wasting their money buying it

@John_Hemming

I vote p5p. Pyroxidine self inhibits at high level, but i have not found a reference. 100mg daily is enough to cause this.

If you ingest P-5-P it will be completely converted to pyridoxine before absorption. P-5-P is is simply not absorbed and has to be converted to pyridoxine to be absorbed. So buyinng P-5-P is like buying expensive pyridoxine.