Calcium Alpha-ketoglutarate. A Calcium Supplement With Added Benefits?

[agnostic]

While searching for the ideal calcium supplement I came across calcium alpha-ketoglutarate which I think has not been discussed on this forum yet and looks highly interesting. There is a study showing that calcium alpha-ketoglutarate extends lifespan and compresses morbidity in aging mice

Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice
Azar Asadi Shahmirzadi, Daniel Edgar, Chen-Yu Liao, Yueh-Mei Hsu, Mark Lucanic, Arash Asadi Shahmirzadi, Christopher Wiley, Rebeccah Riley, Brian Kaplowitz, Garbo Gan, Chisaka Kuehnemann, Dipa Bhaumik, Judith Campisi, Brian K Kennedy, Gordon J. Lithgow
doi: Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice

Abstract
The decline in early life mortality since the 1950s has resulted in dramatic demographic shift towards aged population. Aging manifests as a decline in health, multiple organ dysfunction and increased vulnerability to diseases, which degrades quality of life. A verity of genetic and pharmacological interventions, mostly from non-vertebrate models, have been identified that can enhance lifespan. Whether these interventions extend healthspan, the disease free and functional period of life, has only sometimes been tested and is often a matter of debate. Human aging indices have been developed to assess elements of functional decline with aging (e.g. sarcopenia, cognitive function). However, corresponding comprehensive indices in mice are seldom applied to aging studies. To probe the relationship between healthspan and lifespan extension in mammals, we performed a series of longitudinal, clinically-relevant healthspan measurements. Metabolism and aging are tightly connected and specific perturbations of nutrient-sensing pathways can enhance longevity in laboratory animals. Here we show that alpha-ketoglutarate (delivered in the form of a Calcium salt, CaAKG), a key metabolite in tricarboxylic (TCA) cycle that is reported to extend lifespan in worms, can significantly extend lifespan and healthspan in mice. AKG is involved in various fundamental processes including collagen synthesis and epigenetic changes. Due to its broad roles in multiple biological processes, AKG has been a subject of interest for researchers in various fields. AKG also influences several age-related processes, including stem cell proliferation and osteoporosis. To determine its role in mammalian aging, we administered CaAKG in 18 months old mice and determined its effect on the onset of frailty and survival, discovering that the metabolite promotes longer, healthier life associated with a decrease in levels of inflammatory factors. Interestingly the reduction in frailty was more dramatic than the increase in lifespan, leading us to propose that CaAKG compresses morbidity.

Calcium alpha-ketoglutarate is also a good phosphate binder and effectively treats secondary hyperparathyroidsm:

Miner Electrolyte Metab . 1996;22(1-3):196-9.

Long-term Treatment With Calcium-Alpha-Ketoglutarate Corrects Secondary Hyperparathyroidism

E Zimmermann, S Wassmer, V Steudle

Calcium-alpha-ketoglutarate (Ca-ket) is known as a highly effective phosphate (P) binder in hemodialysis (HD) patients. In addition, alpha-ketoglutarate has been shown to improve metabolic alterations. We investigated the effect of long-term P-binding therapy with Ca-ket to determine whether P accumulation is the main reason of secondary hyperparathyroidism (HPT) in HD patients or not. Ca-ket was prescribed to 14 HD patients as a soluble preparation in a mean dosage of 4.5 g/day (0.975 g elemental Ca) for a period of 36 months. Serum P continuously dropped from prestudy 2.6 +/- 0.1 (mean +/- SEM) to 1.9 +/- 0.07 mmol/l (p < 0.001), whereas serum Ca increased from 2.2 +/- 0.1 to 2.47 +/- 0.08 mmol/l (p < 0.05). Thus, Ca/P ratio in serum converted significantly from 0.91 +/- 0.02 (prestudy) to 1.28 +/- 0.01 (p < 0.001). Intact parathyroid hormone (iPTH) continuously normalized in all patients from 29 +/- 5 to 8 +/- 2 pmol/l (p < 0.001). The present data show that long-term treatment with Ca-ket normalizes secondary HPT by simultaneously P binding and correcting Ca/P ratio in serum without vitamin D treatment.

Alpha-ketoglutarate also lowers ammonia and has antioxidant functions. For review, see

Review Article | Open Access

Volume 2018 |Article ID 3408467 | 6 pages | The Antioxidative Function of Alpha-Ketoglutarate and Its Applications
The Antioxidative Function of Alpha-Ketoglutarate and Its Applications
Shaojuan Liu,1,2 Liuqin He,1,2 and Kang Yao1


Academic Editor: Lidong Zhai
Received04 Jan 2018
Accepted19 Feb 2018
Published21 Mar 2018
Abstract
Alpha-ketoglutarate (AKG) is a crucial intermediate of the Krebs cycle and plays a critical role in multiple metabolic processes in animals and humans. Of note, AKG contributes to the oxidation of nutrients (i.e., amino acids, glucose, fatty acids) and then provides energy for cell processes. As a precursor of glutamate and glutamine, AKG acts as an antioxidant agent as it directly reacts with hydrogen peroxide with formation of succinate, water, and carbon dioxide; meanwhile, it discharges plenty of ATP by oxidative decarboxylation. Recent studies also show that AKG has alleviative effect on oxidative stress as a source of energy and an antioxidant in mammalian cells. In this review, we highlight recent advances in the antioxidative function of AKG and its applications in animals and humans.

Furthermore, it seems to have positive effect on the microbiome and to lower intestinal inflammation:
The effects of dietary supplementation with α-ketoglutarate on the intestinal microbiota, metabolic profiles, and ammonia levels in growing pigs - ScienceDirect
Europe PMC
Alpha-ketoglutarate suppresses the NF-κB-mediated inflammatory pathway and enhances the PXR-regulated detoxification pathway


Unfortunately, I couldn't find pure calcium alpha-ketoglutarate as a supplement. If anyone can find it let me know. The only products with calcium alpha-ketoglutarate I could find are the following:
Alpha Ketoglutaric Acid 300 mg - Hypoallergenic from Kirkman
Calcium AKG
https://rejuvant.com/f/Mens-Ingredients.jpg

They all contain problematic fillers.

 

[agnostic]

I asked Ray Peat about it and he agreed that is sounds very good.

 

[Broken man]

I asked Ray Peat about it and he agreed that is sounds very good.

Thank you So much .....

 

[ddjd]

does this have it?

https://www.amazon.com/Kirkman-Alph...ium+alpha-ketoglutarate&qid=1592229422&sr=8-6

 

[Broken man]

does this have it?

https://www.amazon.com/Kirkman-Alph...ium+alpha-ketoglutarate&qid=1592229422&sr=8-6

Silicon dioxide, not good.

 

[agnostic]

This company sells calcium alpha-ketoglutarate as pure powder:
Calcium Alpha-Ketoglutarate 21%

If you buy 5 kg, it costs about 25 dollars per kg. They also sent me a certificate of analysis showing that it is essentially free of contaminants. Unfortunately, they only sell to other businesses.

@LifeGivingStore
@healthnatura

Could you make this available in your store?

 

[not_James_Bond]

@agnostic
What about this https://www.amazon.com/SIMPLESA-NUT...01284XB4W/ref=cm_cr_arp_d_product_top?ie=UTF8

 

[agnostic]

@not_James_Bond

It contains silicon dioxide and it's ridiculously expensive (57 dollars for 108 grams of calcium alpha ketoglutarate).

 

[Dave Clark]

@not_James_Bond

It contains silicon dioxide and it's ridiculously expensive (57 dollars for 108 grams of calcium alpha ketoglutarate).

It seems this works out about the same as the Kirkmans and the others, if my math is right. This looks promising. Is there any issues with glutamine and brain with this, regarding exitotoxicity?

 

[agnostic]

Alpha-ketoglutaric acid was introduced to the supplement market in the early eighties by Dr. Jon Pangborn, who used it to lower high ammonia levels in his autistic son. Pangborn has written the book "Nutrional Supplement Use for Autistic Spectrum Disorder", which I can highly recommend.

Here is an excerpt from the chapter about alpha-ketoglutaric acid:


Alpha-Ketoglutaric Acid

Alpha-ketoglutaric acid (or "alpha-ketoglutarate") is an extremely important organic acid needed for nitrogen balance, especially in the brain and CNS. It is also a critical component of the energy conversion in cell mitochondria, and it is part of the mitochondrial antioxidant mechanism.


Indications of Need

A diagnosis of or signs consistent with: ammonia excess, hyperammonemia, blood nitrogen or nitrogen compound excess; exposure to excesses of arsenic, mercury, lead or antimony; exposure to xenobiotic chemicals (pesticides, herbicides, fungicides, anesthetics petrochemicals, combustion fumes/smoke, nitriles or cyanide); stool too basic (pH too high - ammonia from dysbiosis); diagnosis of mitochondrial disorder, oxidant stress.


When and How Much?

This depends on the problem and the reason for its use. Alpha-ketoglutaric acid does not stop excessive formation of ammonia, rather, it extends cell and tissue abilities to cope with ammonia. It chemically combines with ammonia to form glutamic acid - a much less toxic substance than ammonia. If ammonia excess is the problem, gram quantities per day of alpha-ketoglutarate (buffered) can be beneficial 50 to 200 mg per Kg body weight. A taurine supplement might help further by encouraging the conversion of glutamic acid to glutamine. Lesser amounts of alpha-ketoglutaric acid, 25 to100 mg/kg may be helpful for other problems. Usually, this nutrient is available in capsules of 300 milligrams buffered to prevent acidity. Divided doses with meals works best; do not use unbuffered alpha-ketoglutaric acid.


Adverse Response to Alpha-Ketoglutaric Acid.

Since the beginnings of its use as a nutritional product in the early 1980s, there have been no reports of problems that I know of, with two exceptions. The first was a teenager who took a whole 100-capsule bottle of 300 mg capsules in one day. That's 30 grams. He exhibited hyperactivity for the next 24 hours but had no other symptoms. The second was nausea traced to poor product quality. During manufacturing, storage and use, alpha-ketoglutaric acid should be kept dry with the bottle tightly closed. If the product is dark colored (instead of a white powder), or if it smells bad (fishy or foul), do not use it.


About Alpha-Ketoglutaric Acid (Optional Reading)

In the 1980s, our son was diagnosed as having elevated ammonia in blood but without a problem in urea formation and without evident dysbiosis. Something in bis metabolism wasn't going right, and the two doctors in charge were baffled. We followed instructions and lowered his dietary protein intake, and I decided to investigate further. I hit the books, and an interesting find came from Albert Lehninger’s famous textbook, Biochemistry. Lehninger was a professor of medicine at Johns Hopkins University. The find was that the body has its own remedy for ammonia besides the liver's urea cycle. In fact, in the brain and central nervous system, this remedy is the major pathway of ammonia disposal. Here’s how it works.

In the brain, some alpha-ketoglutaric acid combines with ammonia to make glutamic acid. This is what’s supposed to happen. The brain doesn’t have direct access to a urea forming cycle as the liver does. So the brain needs a fast, efficient alternative. After the glutamic acid is made, we still have a problem. Glutamic acid is very slow to cross the brain-blood barrier, it’s an excitatory neurotransmitter, and too much of it causes trouble. To counter the problem, the brain has a second step to its ammonia detoxification process. It adds another ammonia (as an “amide”) to glutamic acid. That changes it into glutamine. This is the step that taurine promotes.

Glutamine, with its ammonia load aboard, readily passes out the brain. Via blood, it goes to the kidneys for excretion, or it’s disassembled and the resulting ammonia is changed into urea in the liver.

So, my problem was to come up with some alpha-ketoglutaric acid. It was not available anywhere as a nutritional supplement (~1980). It was available as a specialty chemical; it is a natural, big-time chemical in our bodies, but its use in humans seemed to only be in clinical research studies. Nobody would make the jump from research uses to nutritional supplement use.

It took over a year, but finally someone came along who could help – Mr. Jim Dews. Jim operated a nutritional supplement company in Texas, and he custom-made various nutritional products for doctors. We put our heads together; he came up with a buffering formulation, and then made a pilot batch. He and I took several capsules without ill effect. My family, Dews' employees, and some of Dr. Philpott's staff in Oklahoma City also tried it. ln the 1980s, Dr. Philpott was one of our son's physicians. Eventually, since it was a natural biochemical in the body, he selected some patients to try it. In most cases, the feedback was - Wow! Where'd this extra energy come from!

Lab tests followed, showing that blood ammonia levels are lowered by alpha-ketoglutaric acid supplements. In fact, normal alpha-ketoglutaric acid levels become abnormally low when ammonia is elevated. There even was a contemporary article from the New England Journal of Medicine showing exactly this for individuals with a metabolic fault to the urea cycle - Batshaw ML, Roan Y et al. "Cerebra! Dysfunction in Asymptomatic Carriers of Ornithine Transcarbamylase Deficiency", NEJ Med 302 no. 9 (Feb 28, 1980) 482-85; see Fig 4, p 484.

So, giving alpha-ketoglutaric acid pretty much has to work as a nutritional strategy for elevated ammonia. We didn’t try to patent alpha-ketoglutarate. After Jim Dews had it exclusively for about two years, I got Klaire Labs to manufacture it, too. After that, it grew on its own.

Inside cells there are several chemical processes that make and use alpha-ketoglutaric acid. One such process inside cell mitochondria is called the “citric acid cycle” – it’s an energy conversion, acid-base balancing and coenzyme-activating mechanism. Another process is the called the “malate shuttle”. In that one, alpha-ketoglutarate travels out of the mitochondria, goes through hydrogen addition and goes back in as malic acid. That’s a major process for antioxidant protection (hydrogen delivery) for mitochondria.

Inside mitochondria, in the citric acid cycle, alpha-ketoglutaric and coenzyme A are changed into succinyl-coenzyme A by an enzyme complex that forms activated niacin coenzyme, NADH, as well as CO2 (for bicarbonate). The succinyl CoA, by the way, is what vitamin B12 as adenosylcobalamin assists in making from methylmalonyl-CoA (MMA-CoA); methylmalonic acid comes from propionic acid. See Vitamin chapter, B12 section. So, the mitochondrial chemistry of alpha-ketoglutaric acid, vitamin B12 and carnitine are all closely related.

 

[Dave Clark]

Alpha-ketoglutaric acid was introduced to the supplement market in the early eighties by Dr. Jon Pangborn, who used it to lower high ammonia levels in his autistic son. Pangborn has written the book "Nutrional Supplement Use for Autistic Spectrum Disorder", which I can highly recommend.

Here is an excerpt from the chapter about alpha-ketoglutaric acid:


Alpha-Ketoglutaric Acid

Alpha-ketoglutaric acid (or "alpha-ketoglutarate") is an extremely important organic acid needed for nitrogen balance, especially in the brain and CNS. It is also a critical component of the energy conversion in cell mitochondria, and it is part of the mitochondrial antioxidant mechanism.


Indications of Need

A diagnosis of or signs consistent with: ammonia excess, hyperammonemia, blood nitrogen or nitrogen compound excess; exposure to excesses of arsenic, mercury, lead or antimony; exposure to xenobiotic chemicals (pesticides, herbicides, fungicides, anesthetics petrochemicals, combustion fumes/smoke, nitriles or cyanide); stool too basic (pH too high - ammonia from dysbiosis); diagnosis of mitochondrial disorder, oxidant stress.


When and How Much?

This depends on the problem and the reason for its use. Alpha-ketoglutaric acid does not stop excessive formation of ammonia, rather, it extends cell and tissue abilities to cope with ammonia. It chemically combines with ammonia to form glutamic acid - a much less toxic substance than ammonia. If ammonia excess is the problem, gram quantities per day of alpha-ketoglutarate (buffered) can be beneficial 50 to 200 mg per Kg body weight. A taurine supplement might help further by encouraging the conversion of glutamic acid to glutamine. Lesser amounts of alpha-ketoglutaric acid, 25 to100 mg/kg may be helpful for other problems. Usually, this nutrient is available in capsules of 300 milligrams buffered to prevent acidity. Divided doses with meals works best; do not use unbuffered alpha-ketoglutaric acid.


Adverse Response to Alpha-Ketoglutaric Acid.

Since the beginnings of its use as a nutritional product in the early 1980s, there have been no reports of problems that I know of, with two exceptions. The first was a teenager who took a whole 100-capsule bottle of 300 mg capsules in one day. That's 30 grams. He exhibited hyperactivity for the next 24 hours but had no other symptoms. The second was nausea traced to poor product quality. During manufacturing, storage and use, alpha-ketoglutaric acid should be kept dry with the bottle tightly closed. If the product is dark colored (instead of a white powder), or if it smells bad (fishy or foul), do not use it.


About Alpha-Ketoglutaric Acid (Optional Reading)

In the 1980s, our son was diagnosed as having elevated ammonia in blood but without a problem in urea formation and without evident dysbiosis. Something in bis metabolism wasn't going right, and the two doctors in charge were baffled. We followed instructions and lowered his dietary protein intake, and I decided to investigate further. I hit the books, and an interesting find came from Albert Lehninger’s famous textbook, Biochemistry. Lehninger was a professor of medicine at Johns Hopkins University. The find was that the body has its own remedy for ammonia besides the liver's urea cycle. In fact, in the brain and central nervous system, this remedy is the major pathway of ammonia disposal. Here’s how it works.

In the brain, some alpha-ketoglutaric acid combines with ammonia to make glutamic acid. This is what’s supposed to happen. The brain doesn’t have direct access to a urea forming cycle as the liver does. So the brain needs a fast, efficient alternative. After the glutamic acid is made, we still have a problem. Glutamic acid is very slow to cross the brain-blood barrier, it’s an excitatory neurotransmitter, and too much of it causes trouble. To counter the problem, the brain has a second step to its ammonia detoxification process. It adds another ammonia (as an “amide”) to glutamic acid. That changes it into glutamine. This is the step that taurine promotes.

Glutamine, with its ammonia load aboard, readily passes out the brain. Via blood, it goes to the kidneys for excretion, or it’s disassembled and the resulting ammonia is changed into urea in the liver.

So, my problem was to come up with some alpha-ketoglutaric acid. It was not available anywhere as a nutritional supplement (~1980). It was available as a specialty chemical; it is a natural, big-time chemical in our bodies, but its use in humans seemed to only be in clinical research studies. Nobody would make the jump from research uses to nutritional supplement use.

It took over a year, but finally someone came along who could help – Mr. Jim Dews. Jim operated a nutritional supplement company in Texas, and he custom-made various nutritional products for doctors. We put our heads together; he came up with a buffering formulation, and then made a pilot batch. He and I took several capsules without ill effect. My family, Dews' employees, and some of Dr. Philpott's staff in Oklahoma City also tried it. ln the 1980s, Dr. Philpott was one of our son's physicians. Eventually, since it was a natural biochemical in the body, he selected some patients to try it. In most cases, the feedback was - Wow! Where'd this extra energy come from!

Lab tests followed, showing that blood ammonia levels are lowered by alpha-ketoglutaric acid supplements. In fact, normal alpha-ketoglutaric acid levels become abnormally low when ammonia is elevated. There even was a contemporary article from the New England Journal of Medicine showing exactly this for individuals with a metabolic fault to the urea cycle - Batshaw ML, Roan Y et al. "Cerebra! Dysfunction in Asymptomatic Carriers of Ornithine Transcarbamylase Deficiency", NEJ Med 302 no. 9 (Feb 28, 1980) 482-85; see Fig 4, p 484.

So, giving alpha-ketoglutaric acid pretty much has to work as a nutritional strategy for elevated ammonia. We didn’t try to patent alpha-ketoglutarate. After Jim Dews had it exclusively for about two years, I got Klaire Labs to manufacture it, too. After that, it grew on its own.

Inside cells there are several chemical processes that make and use alpha-ketoglutaric acid. One such process inside cell mitochondria is called the “citric acid cycle” – it’s an energy conversion, acid-base balancing and coenzyme-activating mechanism. Another process is the called the “malate shuttle”. In that one, alpha-ketoglutarate travels out of the mitochondria, goes through hydrogen addition and goes back in as malic acid. That’s a major process for antioxidant protection (hydrogen delivery) for mitochondria.

Inside mitochondria, in the citric acid cycle, alpha-ketoglutaric and coenzyme A are changed into succinyl-coenzyme A by an enzyme complex that forms activated niacin coenzyme, NADH, as well as CO2 (for bicarbonate). The succinyl CoA, by the way, is what vitamin B12 as adenosylcobalamin assists in making from methylmalonyl-CoA (MMA-CoA); methylmalonic acid comes from propionic acid. See Vitamin chapter, B12 section. So, the mitochondrial chemistry of alpha-ketoglutaric acid, vitamin B12 and carnitine are all closely related.

Thanks for the post, it answers my question on exitotoxicity. I have dealt with mercury amalgams in the past, so based on the Indications of Needs, I think it would be beneficial for me, and maybe for just about anybody since we are all exposed to the chemicals mentioned. I can see why Dr. Peat likes the AKG since it binds to and lowers phosphates, etc. I suppose if he did not say anything negative about it, that it may not raise estrogen, etc. Definitely one I will give a try. I used to use arginine AKG when I thought raising growth hormone was good, but haven't done that for years, but will try the calcium form now,

 

[agnostic]

There is also a special type of creatine that is bound to alpha ketoglutaric acid. This one has no fillers:
https://www.amazon.com/Good-State-Creatine-Alpha-Ketoglutarate-capsule/dp/B007I6NGAK

 

[not_James_Bond]

@Dave Clark
Please update this thread if you do try it out, thanks.

 

[Dave Clark]

There is also a special type of creatine that is bound to alpha ketoglutaric acid. This one has no fillers:
https://www.amazon.com/Good-State-Creatine-Alpha-Ketoglutarate-capsule/dp/B007I6NGAK

Thanks for that tip. I do use creatine, and noticed an improvement in my digestive system, which is what I had read about it. Wondering now whether I should get this combo compound or use them separately. I suppose I will try both. And, 007, I will update my experience with the AKG.

 

[Pointless]

I tried creatine alpha-ketoglutarate for the past week. I hoped it would improve leaky gut and Crohn's disease. The most noticeable effect is that it gives me erections that last 2-3 hours. Some Google searching revealed that alpha-ketoglutarate is a precursor to nitric oxide. I figured Ray would know something like this, but maybe he just looked at the studies that were sent to him? So I'm a bit confused by this compound.

 

[not_James_Bond]

@Dave Clark
Any updates?
@Pointless That's an interesting side effect, lol

 

[Dave Clark]

@Dave Clark
Any updates?
@Pointless That's an interesting side effect, lol

About two weeks at one capsule/day. No issues with its use. If anything, a bit more fluid energy level, but it is hard to say if it is from that, but correlates to when I started using it. I will continue with one cap/day unless I see recommendations to use more. I decided for now to just use my creatine separately, instead of getting that form of AKG.

 

[Jessie]

If I'm not mistaken, alpha ketoglutaric is one of the primary ketoacids found in cooked potato juice. I've made this several times and it's always been quite tasty. Several steps involved, but the steps are easy. I just blend roughly 4-5lbs of potatoes in the vitamix with a little water, then strain through metal screen and cheesecloth.

All that goodness that settles in the bottom, the white powdery looking stuff, is the ketoacids. After you cook it for like 45min-1hr it reduces down into a thick soup like consistency. Very minimal amounts of starch, so it won't likely disrupt the digestive tract.

The one downside is there's a lot of waste. The yield return from 5lbs of potatoes isn't very much. I'd imagine this isn't very economical for someone wanting to use it as their primary source of protein. Even doing it once a day could turn out to be quite expensive if you're going to the store to buy potatoes every few days.

 

[agnostic]

I have now ordered 5 kg pure calcium alpha-ketoglutarate from Monarch nutraceuticals. It's dirt cheap compared other products on the market and costs only 25 dollar per kg if you order at least 5 kg.
Calcium Alpha-Ketoglutarate 21%

They only sell to other businesses, but a friend of mine who has his own business could order it for me.

Since about 1 week I've been taking 1.5 grams twice per day. The taste isn't too bad (slightly sour), but I fill it into 000 capsules for convenience. I haven't noticed much from it, neither negative nor positive.

 

[Dave Clark]

I have now ordered 5 kg pure calcium alpha-ketoglutarate from Monarch nutraceuticals. It's dirt cheap compared other products on the market and costs only 25 dollar per kg if you order at least 5 kg.
Calcium Alpha-Ketoglutarate 21%

They only sell to other businesses, but a friend of mine who has his own business could order it for me.

Since about 1 week I've been taking 1.5 grams twice per day. The taste isn't too bad (slightly sour), but I fill it into 000 capsules for convenience. I haven't noticed much from it, neither negative nor positive.

At the rate you are taking it, that is a large supply that looks like about ten years worth, if I am seeing this correctly. How will you store this, and do you think it will keep its potency?