This section answers some of the most interesting questions we've received. You may find them useful in helping you with some of your needs. Indeed, you may find the exact same question you want to ask - answered right here! (You can always use the search facility to aid you, especially as this area is likely to grow in size). As usual all educational information is offered under the IAS Terms and Conditions.
Whatever happened to Vasopressin and how is Desmopressin able to take its place?
I'm very interested in these new carnosine eye-drops that the Russian's claim cure cataract in a few months for most people. Can you tell me anymore about them?
I have been reading about carnosine's ability to treat and prevent cataract. Is this because it helps break cross-links as well as prevent them? If so, isn't this more likely at the higher dosages of 1g being recommended by LEF, rather than the 50-100mg you are advocating?
What do most anti-aging physicians consider the cause of aging to be?
You have written that along with Metformin, that Dilantin ® is also useful as an insulin sensitizer. Is either one or the other better for this purpose, and how about potential side effects? Also can these be taken safely with meals during days that HGH is being injected?
Isn't calorie restriction as reported by Professor Roy Walford in his book The 120 Year Diet, the only really proven method of life extension?
Lately, I've been hearing about aniracetam as an alternative to piracetam. Has anybody tried aniracetam and found it better? How?
Why hasn't IAS stocked any of the Growth Hormone (GH) supplements that have become available all over the place in the US?
Your SAMe seems expensive compared to some brands I've seen in the States, why is that?
What's the difference between deprenyl HCL tablets and deprenyl citrate liquid?
What's the status of GHB?
Q. Whatever happened to Vasopressin and how is Desmopressin able to take its place?
A. Vasopressin is a peptide hormone believed to be responsible for the deposit of memories in the area of the brain called the hippocampus. It is also known to control the bladder, and hence one of its approved uses is to use it as a nasal spray, to help control frequent urination (it helps to conserve water). However, Vasopressin as a pharmaceutical agent was of porcine origin, and it has since been replaced by Desmopressin. Desmopressin is a synthetic version (i.e. made up of chemicals in the lab), and whilst it is a very similar molecule, it is true to say that it is not exactly the same. For example, Desmopressin seems to be more potent, with action on additional receptors, however the worldwide commercial producers of Vasopressin, have on-mass converted to Desmopressin. I cannot tell you exactly why this is, perhaps it is a preference for a "cleaner" product, i.e. a synthetic one. So until we can obtain Vasopressin per-se, we shall market Desmopressin as its direct replacement. Further details about Desmopressin/ Vasopressin can be seen by clicking here.
Phil Micans PharmB
Q. I'm very interested in these new carnosine eye-drops that the Russians claim cure cataract in a few months for most people. Can you tell me anymore about them?
A. Recently IAS has placed a considerable amount of information about this new eye-drop which contains n-acetylcarnosine (or NAC) onto this website. We also feel this is a very exciting and important breakthrough for the treatment and prevention of senile cataract. There is a big difference between NAC and L-carnosine (which is the more common variety of carnosine), and reports indicate that L-carnosine as an eye-drop may be harmful in long term use. The Russians have developed the anti-cataract eye-drop of NAC in conjunction with a Japanese pharmaceutical company and they have a proprietary method of producing a most pure form of NAC. They tried other makers NAC's and combinations of formulas and found that they were ineffective against cataract, so it appears to be a very precise requirement. Therefore, we highly recommend reading the following material.
1. To read about how NAC has been used against cataract (and the problems of cataract in general), read Dr. Mason's article by clicking here. 2. To read about the important differences of NAC eye-drops and L-carnosine eye-drops, read Dr. Babizhayev's interview by clicking here. 3. To read more about why only a special kind of NAC has been shown to be effective, and why changes to the formula of excipients and additional ingredients can prevent NAC from being effective, click here. 4. To read about the difference in the use of oral types of carnosine, read Dr. Kyriazis' article by clicking here.
Q. I have been reading about carnosine's ability to treat and prevent cataract. Is this because it helps break cross-links as well as prevent them? If so, isn't this more likely at the higher dosages of 1000mg being recommended by LEF, rather than the 100-300mg you are advocating?
A. I think we should be aware that the Carnosine eye-drops being used in the Russian clinical trials for cataract is a unique form of carnosine called N-Alpha-Acetylcarnosine - it is NOT the L-carnosine that has recently become available in the States (see question above for further details).
The N-Alpha-Acetylcarnosine eye-drops have been used in clinical trials and are virtually eliminating cataract within a 6-12 month period for the majority of patients (dosages have been 2 drops into each eye twice each day), no major side effects or contraindications have been noted to date.
Interestingly, much of the talk in the anti-aging chat-group forums is about a drug development known as ALT-711 and its potential ability to break existing protein cross-links. However, it must be clear by its very treatment of senile cataract that this Russian form of carnosine must also be breaking as well as preventing cross-links too.
Recently Dr. Marios Kyriazis and Dr. Ward Dean and I have shared some thoughts regarding the current trend of "high" dosages of L-carnosine that appear to be currently in vogue. Here is the reply we received from Dr. Kyriazis:
"I have no idea upon what the 1000mg dose is being based. In my experience 50mg to 100mg a day is sufficient, but higher doses of 150mg to 200mg may be used. LEF literature claims that 1000mg mega doses bypass carnisinases degradation, however I ask why is degradation by carnisinases a bad thing? We don't really know where the benefits of carnosine are coming from. Dr. Hipkiss (and I agree with him) believes that some of the benefits of carnosine are derived AFTER carnosine has been degraded by carnisinases to produce histidine and alanine. Some of the benefits may be due to these amino acids, particularly histidine. Other researchers believe that too much carnosine (no dose mentioned!) may produce harmful by products with the possibility of allergic-type reactions. I know of at least one patient who had disturbing muscle twitching after taking the 1000mg dose. Until better studies clarify these issues, I prefer to stay on the safe side and use carnosine at the existing dosage of 50-100mg daily."
Since that time Dr. Kyriazis has undertaken a small clinical trial to evaluate carnosine supplementation. You may click here to see these results which show that dosages of carnosine are effective at 100mg to 200mg per day and that dosages in excess of 500mg may be less effective.
There is now also a mass of information about N-acetylcarnosine available at www.nacetylcarnosine.com
Phil Micans PharmB
Q. What do most anti-aging physicians consider the cause of aging to be?
A. The main premise of aging centers on the impact of free-radicals, which are basically unstable molecules that collide with others and end up damaging cell structures and indeed DNA. Therefore, the question must be asked how are free-radicals generated? Of course they can be generated by pollutants and radiation, but simple eating, breathing and drinking also causes their formation, alas oxygen is a very potent free radical generator.
In particular, free radicals are very damaging in the mitochondria, the tiny powerhouses that generate all of our energy. As such, over time these mitochondria become larger, fewer and less efficient, a part of anti-aging medicine is to support, enhance and protect mitochondrial structure and performance. Of particular use are Hydergine, Acetyl-L-Carnitine, ATP, NADH, CoQ10 and Idebenone.
There is also the glycosylation action. This is where oxygen reacts with glucose to bind proteins and impair cell structure. This is probably the primary cause of hardening arteries, skin discoloration and thickening and the formation of cataract. Products that show promise in this regard are Aminoguanidine, the Carnosines and Acetyl-L-Carnitine.
The Neuroendocrine Theory of Aging focuses on the decline in the endocrine system. This system is responsible for the production of the majority of our hormones. Indeed there is also a loss of sensitivity of cells to hormones. This is a complicated area that would involve specific hormone replacement therapy, but particular focus can be paid to Melatonin which is believed to protect the pineal gland and thus the endocrine system, and also to receptor enhancers such as Metformin or even Adrafinil or its sister Modafinil.
Other accelerators of aging include methylation. This is a process by which enzymes and catalysts are required to convert one chemical to another in the body. A lack of those converters obviously leads to a lack of the required end material/ product. After all, one can have all the materials available to build a house, but until water can be added to the lime and cement, concrete cannot be made etc. Key methylation agents include the B vitamins and SAMe.
Other theories of aging include chronic inflammation and of course the genetic code decline, (i.e. telomeres becoming shorter and thus the blue-prints being damaged and leading to imperfect cell structure). However, even here, the actual cause of the damage may be due to the presence of free radicals.
All the major theories of aging can be read about by clicking here.
Phil Micans PharmB
Q. You have written that along with Metformin, that Dilantin ® is also useful as an insulin sensitizer. Is either one or the other better for this purpose, and how about potential side effects? Also can these be taken safely with meals during days thatHGH is being injected?
A. Comparative studies have not been done. At the low doses of dilantin that we recommend, side effects are generally non-existent. (Dilantin ® 200-300mg daily can significantly improve the Chol/HDL ratio).
I have used Dilantin ® (Phenytoin) and Metformin together for years (and have recommended this regimen to many patients, as well). Dilantin ® and Metformin can be taken with meals or on an empty stomach. Unlike other oral anti-diabetic agents, these substances do not cause hypoglycemia-in fact, they are helpful for those with hypoglycemia, as better use is made of the available glucose.
No problem taking them in conjunction withHGH.
Ward Dean MD
Q. Isn't calorie restriction as reported by Professor Roy Walford in his book The 120 Year Diet, the only really proven method of life extension?
A. Caloric restriction is probably the least-used life extension technique. I've heard people say, "Roy Walford may not live any longer, but it'll sure seem like it!"
I believe that the primary mechanism by which caloric restriction works is that insulin levels are maintained at a low level. Many of the same benefits of caloric restriction can be obtained by insulin receptor sensitizers like Metformin, Phenformin, and probably Aminoguanidine and perhaps also ALT-711. Plus, "starch blockers" like Acarbose (aka Glucobay ®) are additive in their insulin-lowering effects to Metformin.
Professor Vladimir Dilman demonstrated an extension of maximum life span in experimental animals using Phenformin (an analog of Metformin).
Ward Dean MD
I'll add that caloric restriction also leads to reduced numbers of free radicals, and as the free radical theory of aging is perhaps one of the "most" proven theories of aging, this would also benefit longevity. Alas, eating, drinking and breathing generate free radicals and none of us are going to stop doing any of these things! Another answer must lie in the use of a broad spectrum of anti-oxidants.
Phil Micans PharmB
Q. Lately, I've been hearing about aniracetam as an alternative to piracetam. Has anybody tried aniracetam and found it better? How?
A. There are 3 commercially available analogues to Piracetam. They are Aniracetam, Oxiracetam and Pramiracetam. The most "different" chemically speaking is pramiracetam and the "least" is Oxiracetam.
Aniracetam and Pramiracetam are more fat than water soluble (compared to Piracetam and Oxiracetam) and as a result the half-life of the drug is longer. In other words the effects last longer. The differences between all the analogues are more subjective and individual and therefore there is no set "this will do that and that will do this etc."
All the analogues of Piracetam are more potent than it (when compared mg to mg). For example one study suggested that the optimal maximum dose of Piracetam was 100mg per Kg body weight (that's 2.2 Lbs.), but Pramiracetam was found to be as effective at 15mg per Kg body weight (a difference of more than 6x).
There is also evidence that Aniracetam displays the most stimulatory affect upon brain AMPA receptors and that the piracetam analogues may exert more brain hemispheric intercommunication across the corpus callosum (thereby improving ying and yang).
That's the good news, the bad news is that all the analogues are considerably more expensive than Piracetam! The analogues of Piracetam are also not made on a regular basis, and from time to time become temporarily unavailable.
On a personal note I prefer aniracetam and it is also the nootropic drug of choice in Japan. Attention and vigilance are improved over piracetam and as I say the effects last longer after taking the pills.
However, as is so true of much of mental enhancement and indeed anti-aging medicine some careful individual experimentation is probably required to determine which one is best for you.
Phil Micans PharmB
Q. Why hasn't IAS stocked any of the Growth Hormone (GH) supplements that have become available all over the place in the US?
A. IAS has a policy of only stocking independently clinically proven products of the highest caliber. To date we have not been satisfied that any of the GH supplement products we've seen meet that standard.
The fact remains thatHGH (Human Growth Hormone) is a complicated chemical consisting of a 191-amino acid chain. Although some recent evidence suggests that folded proteins can penetrate cell membranes when used sublingually (Milstein S.J. et al: Partially unfolded proteins efficiently penetrate cell membranes- implications for oral drug delivery: Journal of Controlled Release 53, 1998, 259-267), I remain unconvinced that GH can be effectively administered via this route.
The multi-billion Dollar pharmaceutical companies were unable to produce a room temperature stable product and an administration only possible via injection. Yet, we are given to believe that multi-thousand Dollar nutritional companies have found the key by producing a stable product that can be taken either orally or sublingual! Is it any surprise that most of the companies offering such products also seem to be of the MLM type?
Some of the products on the market claim to contain actual GH in the bottle (other than the usual agonist chemicals), GH is either a prescription or indeed in some countries a controlled substance, why are these products available over-the-counter if that is the case? Of course some claim homeopathic levels of GH, and that is another story, as a pharmacologist I am unsure about homeopathy although I remain open minded.
It is known that several substances are effective agonists of GH (i.e. they stimulate the pituitary gland's release of GH). These are certainly more proven and a better route to take. Here one may find Ronald Klatz MD's book, Grow Young With HGH (published by Harper Collins), a useful reference guide; in it he lists several beneficial substances.
But in most cases the best that can be expected is about a 30% night time improvement of GH levels, sounds impressive in-itself until one realizes that s.c. injections of GH can make improvements of up to 600%! The best proven oral agonist of GH was Gamma Hydroxy Butyrate (GHB), and it was no accident that GHB's sleep inducing affects must have contributed to its up-to 300% improvement of GH levels (as clinically studied by the Japanese). However the FDA and DEA ban on GHB because of its so-called "Date Rape" properties (and the UN's enforcement of that unscientific evidence in many other countries around the world), effectively rules out that "miracle molecule."
The Australians studied the GH releasing affects of a yeast extract called Vegemite( (the same thing is called Bovril ® in the UK- I don't believe such a product exists in the US). It was found that a night time drink of a couple of teaspoons of this vitamin B rich beef extract improved GH levels by approximately 30%, about as much as these expensively touted "revolutionary" GH supplements! But of course Bovril ® costs cents per drink instead of Dollars, I can confirm however that it doesn't taste very good and is one of those traditional drinks that Grandma always swore by! Interestingly the Australian trials confirmed that the only side effects were drop-outs due to the bad taste!
Dr. Dean will also tell you that his favorite tipple is the traditional dark brown British beer (such as Newcastle Brown), due to their sleep enhancement properties and potential GH release. Although to the best of my knowledge these haven't been clinically studied (unlike the beef yeast extract), they do have one thing in common. They are relatively "high" in GHB content! Obviously this has failed to come to the attention of the DEA, yet.....
I appreciate that everyone is looking for a cheaper way to improve their GH and indeed IGF-1 levels. Injectable GH still remains a relatively expensive anti-aging therapy, even though that cost has been reduced dramatically in recent years due to mass production. It appears that the age related decline of GH has more to do with the release mechanism from the pituitary gland rather than the actual production of GH itself. We also know of some physicians and their patients who inject GH and yet are unable to make a significant impact upon their IGF-1 levels, there are obviously several endocrine mechanisms at play that have not yet been fully elucidated. There are other routes, such as injectable IGF-1, or even hypothalamus peptides (which in our opinion could be the future) such as somatorelin which are commercially available, and others which aren't yet. However, their use is not as proven as GH and their current minute production means that their cost is much greater than injectable GH.
But there are other interesting developments. Rumors abound that Eli-Lilly have developed a nasal spray with a carrier suitable for GH. This form may be nearly as effective as injectable versions, (nasal applications are known to be a close second to injections in terms of their strength) and may be a lot more stable and a lot less temperature sensitive. IAS is following this carefully, and if all goes well we hope to offer such a product as soon as it becomes commercially available.
Phil Micans PharmB
Q. Your SAMe seems expensive compared to some brands I've seen in the States, why is that?
A. I think is often difficult to compare products within the supplement and even drug industry, at least on the surface. For while they appear to be the same, often they are not.
There is a particular problem with SAMe. It is a difficult substance to manufacture and hence that is reflected in its price. However, it is not possible to cut corners with this chemical as it will have a detrimental affect upon its effectiveness. Allow me to elaborate.
Firstly, SAMe is damaged by light, therefore exposure to it begins a destruction process of the active ingredient. The correct way to package SAMe is individually within metal foil, therefore as each tablet is withdrawn for use it does not affect the others (unlike a bottle which would expose the other tablets to light as it is opened). I have even seen one well known vitamin manufacturer present SAMe in glass bottles!
Secondly, SAMe must be enteric coated, this is normally achieved in a tablet form and helps prevent the stomach acids from destroying the product. Some of the supplemental SAMe products are in capsule form, it is possible to have enteric coated capsules (although more unusual), so you should check carefully to make sure they are enteric coated.
Thirdly, SAMe dosages have to be quite high to be effective, I would suggest that a minimum dose of 200mg is at the bottom of the scale with 300mg to 500mg showing much more efficacy. Yet there are SAMe supplements on the market at 50mg, that's a lot of tablets to take each day to be of use.
Fourthly, and perhaps most importantly some manufacturers quote the entire tablet size including the base. This can often mean halving the actual active ingredient, and thus a 400mg tablet is actually 200mg.
Here at IAS we stock the original Italian Samyr ® and Donamet ® brand that was used in the clinical trials that started the "SAMe revolution." The tablets are of course light protected, individual aluminum foil wrapped, enteric coated and each contain what they state of the actual active ingredient.
When working out the cost of a product, multiply the number of tablets by the base and then divide that figure into the price. I have a large American vitamin company's catalog here to hand and they supply 20x 200mg tablets at a "sale" price of $19.95, thus 20x 200 = 4000 and 4g/ 19.95 = $4.99 a gram. The current price for IAS Samyr ® SAMe is 20x 400mg $31.25 which translates to $3.90 a gram, so I truly believe that we are very competitive for such a high quality product.
Phil Micans PharmB
Q. What's the difference between deprenyl HCL tablets and deprenyl citrate liquid?
Deprenyl, otherwise known as selegiline is a well known drug around the world, but its uses for anti-aging and longevity became widely known after a series of animal experiments conducted by the Hungarian scientist Dr. Knoll (see the Monte Carlo Antiaging Conference ™ for further details). He proved that deprenyl supplements could dramatically extend their life span through the ability of deprenyl to support and maintain the age-related loss of a brain neurotransmitter called dopamine.
Nearly all forms of deprenyl are presented in tablets (usually 5mg) formatted in a base of hydrochloride (or HCL), this presents itself as the main drug used treat Parkinson's disease.
Alternatively deprenyl can be bonded in a liquid with citrate to become liquid deprenyl citrate (LDC). Citrate is organic unlike HCL (which is inorganic), furthermore a liquid deprenyl can titrate small doses like 1mg per drop, this can be beneficial for persons who wish to take less than 5mg at one time.
An advantage of the former DEDI LDC lay in their ability to manufacture a very pure form of deprenyl. Most pharmaceutical manufacturers produce deprenyl (selegiline) to between 97% to 98% purity (the remainder contains a minute trace of amphetamine), whereas the DEDI process produces a 99% purity. Another reason why deprenyl HCL tablets are believed to have more side effects than LDC.
Q. What's the status of GHB?
GHB has been condemned by press-releases from the FDA who claim that it is responsible for coma, date-rape and other serious disorders including death. If you bother to read 30-odd years of scientific and clinical research you will surprisingly not learn about any of the above and possibly come to the conclusion that GHB is one of the safest, most benign natural substances that used responsibly within a few basic guidelines (sic).
The American pressure on the WHO has lead them to release edicts about the "dangers of GHB" and thus in turn UN member countries have moved to make GHB a controlled substance. At the time of writing this (August 2003), we understand that the following countries have restricted the availability of GHB, they are Australia, Brunei, Canada, Finland, France, Italy, Japan, New Zealand, Norway, USA, South Africa, Sweden, Switzerland and the United Kingdom.
However, we support science and so we urge you to learn more about the GHB story. Start with biochemist's James South's original extensive GHB article, (with clinical references) that appeared in the Winter 1999 Anti-Aging Bulletin clicking here, (the entire Bulletin can be downloaded from the Bulletin section).
There is also an excellent article written by Ward Dean MD called The Demonization of GHB. You can also view Dr. Dean's correspondence with the American authorities about the classification of GHB in the USA and its grounds by clicking here. (We also highly recommend Dr. Dean's book: GHB, The Natural Mood Enhancer.
Finally, you can see the original general information sheet about GHB that used to be listed under the A-Z Anti-Aging Medicine category, by clicking here.