#61

I think it is possible to have a shortage of oxygen. Sufficient hypoxia causes brain damage.

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#62

yes, Hypoperfusion of the brain is really destructive. As is long-lasting hypoperfusion of other tissues.

#63

I was referring to a shortage of oxygen during normal exercise or athletic activity. Of course people can experience low oxygen environments and die from a lack of oxygen. On a smaller scale blood flow restrictions can cause oxygen deprivation and tissue death.

Are you saying people get brain damage from high intensity exercise?

#64

Normal exercise is OK. However, hypoxia from the air that is breathed can be an issue.

#65

I’m about to start taking citrate and wondered about the blood pressure question and found this paper indicating that the Cl is primarily responsible for increase in blood pressure. This makes me feel better about taking large amounts of sodium citrate.

A limited number of clinical observations also suggest that blood pressure is not increased in humans by high dietary Na+ intake in the absence of Cl−

#66

Be careful taking large amounts of Sodium Citrate. You need to make sure the balance between Sodium and Potassium is correct. It is important to monitor your blood pressure when following this approach.

The balance between the four cations matters.

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#67

I guess large is a relative term. I was worried about trying even a gram per day since the RDA of salt is 1.5 grams.

My plan is to start with a mixture with a ratio of 1000 mg Na/333 mg K /150 mg Mg as you mentioned earlier in the thread and start by taking about 1.5 g of that per day, giving about 1 g of citrate or a little less. I had calcium levels checked recently and was at the high end of the range, so did not plan to include it yet.

Is this still a good ratio to start with? How do you suggest refining the ratio for a given person? Is it as easy as getting Na, K, Mg, and Ca checked via blood test and deciding based on where the values fall within the recommended range?

#68

At lower levels keep an eye on BP when in the stratosphere (like me) watch kidney function.

#69

And watch your ankles for edema. For me smaller frequent doses are better than bigger less frequent doses.

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#70

@John_Hemming How would you improve this summary I made from your long writeup? See questions imbedded below:

Lithium at a roughly 50 micromolar serum concentration. (3-5mg/day of lithium oronate?)

There are a large number of Histone Deacetylase Inhibitors (HDACi s) around. I use them in quartets to minimise the side effects from any one HDACi whilst maximising the HDACi effect. The ones I used tend to have IC50s in the 50 micromolar range (which is not that strong there are nanomolar ones).

My primary quartet is Curcumin, Berberine, Pterostilbene and Quercetin. I have experimented with taking multiple doses in a day (whilst reviewing published research on the maximum sensible dose which has no known negative effects). What is minimum daily dose?

A longevity benefit from eating RNA. What is source (eg, bakers yeast)? Watch purine levels?

Vitamins B12 and B9 are also needed for transcription. I also take Vitamin B5, but that is really for the acetyl-CoA (because B5 is a coa precursor).

Top up melatonin levels though melatonin supplementation during the night. (Dose?)

Take citrate in forms with sodium, potassium and magnesium. Also calcium but not too much. Sodium in isolation would be a mistake. It is important to maintain a ratio of around 3:1 in Sodium - Potassium and slightly less Magnesium. Powder is better than pills.

How much: the weight refered to is the Citrate. The calculation of citrate levels from the cation elemental weight varies for each salt. If you buy the powder then sometimes it is hydrated. If you have the elemental mass you can estimate the mass of citrate by tripling it.

Start small for a week or two with 0.5 grams of citrate. This should have no noticeable effect. You can then increase to 1 grams of citrate. Then 2 grams of citrate. At this stage just make sure your systems can cope (look for swelling of ankles and signs of fighting infection such as pimples).

The next step is to move to 2 grams of citrate the first for breakfast and the second for lunch. Increase as tolerable up to 5g at breakfast and 5g for lunch. It could take 1 year to reach this level.

With the cations you are dosing reasonably heavy amounts of the cations hence you need to check that your kidneys are handling this properly. What I have found it that the supplementation does push sodium, potassium and magesium levels up a bit (eg Na 139->142) , but they drop back really quickly and are always in the normal range. However, this may not be the case for everyone and you need to do blood tests to monitor for this.

Citrate will cause your urine to become more alkaline. My urinary pH has gone up at times to 9.5. It is worth monitoring urinary pH.

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#71

What is missing is the need to do blood tests to monitor particularly renal function. If you start going into higher doses then you need to manage this. I am still working out how best to handle this. Being tea total is probably helpful, but i am not tea total hence it is a bit more complex.

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#72

@John_Hemming
What is the dosing for your quartet?
You take 2mg lithium orotate daily? I’ve head SLGT2 inhibitors knock out 50%

#73

I don’t take an SLGT2 inhibitor, but have dropped back to 1mg elemental lithium anyway

With the initial HDACi quartet it is one of each of the capsules, I can check the capsules if you wish as to dosing, but in the end you are likely to only be able to buy individual capsules in specific dosing.

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#74

Since you measure so much have you thought about running correlations in excel between everything you take and your biomarkers like Lustgarten?

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#75

I have a debugging approach where i test out hypotheses. There are too many variables to rely on basic stats.

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#76

John, have there been any murine studies using citrates?

#77

Not that I know of. There is a drosophila one which showed a small increase and C Elegans had no impact. I think that is because citrates are best when there is an issue with senescent cells. That is not a thing for C Elegans.

There is a lot of experience with short term high citrate dosage in homo sapiens because Sodium Citrate is used as an anti-coagulant.