HeadDoc, Any Thoughts On Selegiline?

[DavidZ]

HeadDoc, do you have any thoughts on Selegiline? I took it for about 5 years in steadily decreasing dosages up until about 2 or 3 months ago.

Selegiline slows the degradation (i.e., extends the life of) dopamine in the brain. A lot of anti-aging doctors believe Selegiline improves/sustains cognition.

[HeadDoc]

David, I haven't used seligiline yet. Here's what I found at LEF.

Age-Associated Mental Impairment


Deprenyl
Another cause of brain aging is the elevation of an enzyme in the brain called monoamine oxidase (MAO). Monoamine oxidase A and B are the primary enzymes that degrade neurotransmitters in the central nervous system and peripheral tissues. Elevated MAO levels damage brain cells and are a specific cause of age-related neuronal deterioration. Too much MAO has also been shown to cause pathological disorders such as Parkinson's disease (Orru et al. 1999; Abell et al. 2000).

Low-dose deprenyl (selegiline) is thought to protect the brain from aging by specifically inhibiting monoamine oxidase B (MAO B) in the brain. Deprenyl was approved for use in Parkinson's disease in the 1980s and was often combined with L-dopa (levodopa). However, one study raised concerns about combining high doses of deprenyl (10 mg per day) with L-dopa due to an apparent increase in mortality in the deprenyl group (Lees 1995). The results of that paper were hotly debated and several flaws were found in the study design. Later studies showed clinical benefit with deprenyl without a decrease in mortality and no toxic effects, particularly when lower doses were used (5 mg a per day or every other day) (LeWitt 1991; Shoulson 1992, 1998).

Deprenyl has long been recommended in very low doses (10 mg a week) as part of an overall anti-aging program because it has been shown to extend lifespan in animal studies. Deprenyl has also been shown to stimulate the efflux of norepinephrine, dopamine, and serotonin in vitro by a direct action on the hypothalamus. Some researchers are proposing that deprenyl may be considered as an alternative to levodopa for starting treatment in Parkinson's disease patients (Caracenia et al. 2001; Mohan Kumar et al. 2001).

Deprenyl has also been shown to induce rapid increases in nitric oxide (NO) production in brain tissue and cerebral blood vessels and also to protect the vascular endothelium from the toxic effects of amyloid-beta peptide (Thomas 2000). Another study showed that deprenyl protected cells from apoptosis induced by a neurotoxin, N-methyl(R)-salsolinol, and reactive oxygen species, nitric oxide and peroxynitrite (Naoi et al. 2000). Additionally, Zhu et al. (2000) showed that deprenyl significantly improved the cognitive function of rats after traumatic brain injury.

A study of 17 patients with Alzheimer's disease found that the Mini-Mental State Examination scores were significantly higher in those patients receiving selegiline (deprenyl) than in those receiving placebo (Alafuzoff et al. 2000). In India, another study of 32 patients with Parkinson's disease found a significant improvement in memory in patients treated with 10 mg a day of deprenyl as compared to placebo (Dixit et al. 1999).

Scientists who conducted lifespan studies using deprenyl have estimated the ideal dose to slow brain aging in humans to be about 1.5 mg daily. Because deprenyl is usually sold in 5-mg tablets and has a long-acting effect on the brain, most Life Extension members take a low dose of 5 mg of deprenyl twice a week.

However, Hydergine seems to be more effective when higher doses are used. European physicians often prescribe 4.5-20 mg daily of Hydergine without concern for toxicity. Persons seeking protection from neurological aging and wanting to boost cognitive function have used high-dose Hydergine and low-dose deprenyl together for more than 16 years. No adverse effects have been reported when using these two medications together.

Care should be taken when administering dopamine to patients who have been using deprenyl (selegiline). One journal article noted a drastic increase in systolic blood pressure after a critically ill man using selegiline was given an infusion of dopamine (Rose et al. 2000).


Nimodipine
Nimodipine is particularly recommended for victims of head trauma. Nimodipine (brand name Nimotop) is a calcium channel blocker specific somewhat selective to the central nervous system. It prevents movement of calcium into the cells of blood vessels, thereby relaxing the vessels and increasing the supply of blood and oxygen. It dramatically improves cerebral blood flow.

Nimodipine is an FDA-approved drug that is used to prevent and treat problems caused by a blood vessel around the brain that has burst. But nimodipine has been ignored by most neurologists treating victims of stroke and other age-related neurological diseases.

An article by Pantoni et al. (2000a) described a 26-week, multinational, double-blind, placebo-controlled study of nimodipine in patients with multi-infarct dementia. This study failed to show a significant effect of nimodipine on cognitive, social, or global assessments. However, a lower incidence of cerebrovascular and cardiac events was observed in the nimodipine-treated patients in comparison with the placebo group. A subgroup analysis found that those patients with subcortical vascular dementia performed better on the majority of neuropsychological tests and functional scales in comparison with patients on placebo (Pantoni et al. 2000b). A recommended dose of nimodipine is 30 mg, three times daily.


Centrophenoxine
Centrophenoxine (meclofenoxate) is widely used in Europe in combination with piracetam to improve memory and enhance mental energy. Although Centrophenoxine is readily available in Europe, it is not sold in the United States. Centrophenoxine can be ordered from pharmacies in Europe.

Researchers have proposed several mechanisms for Centrophenoxine, including:

Increasing activity of free radical scavengers, especially in brain and heart tissues (al-Zuhair et al. 1998)
Providing antioxidant action, possibly due to the DMAE (dimethyl-amino-ethanol) it contains (Zs-Nagy 1989)
Increasing acetylcholinesterase activity in the hippocampus and brain (Sharma et al. 1995)
Decreasing the deposition of the age-pigment lipofuscin, which has been shown to cause neuronal damage (Patro et al. 1992)
Inhibiting total MAO (monoamine oxidase), MAO-A and MAO-B, which has been shown to damage brain cells (Stancheva et al. 1988)
Increasing the content of serotonin (5-HT), a key neurotransmitter that can be damaged by elevated MAO (Stancheva et al. 1988)
Significantly increasing the fluidity of brain membranes, which can reverse the dehydration of nerve cells of older animals (Lustyik et al. 1985; Wood et al. 1986)
Centrophenoxine was shown to improve memory retention in aged rats in tests using the maze method for active avoidance with punishment reinforcement and the step-through method for passive avoidance with negative reinforcement. Centrophenoxine increased the number of responses to conditioned stimulus and strongly prolonged the time spent in the light chamber (a measure of improved retention) (Mosharrof et al. 1987).

A double-blind clinical trial of 50 patients with dementia examined the effects of 2 grams a day of Centrophenoxine for 8 weeks: 48% of the Centrophenoxine group displayed improvements in the memory functions versus 28% of the placebo group (Pek et al. 1989). Another study found that Centrophenoxine corrected the blood pressure drop when standing in 25 patients who had orthostatic hypotension due to brainstem ischemia (Stoica et al. 1991).

The recommended dose of Centrophenoxine is 250-1000 mg daily.


Other Factors to Consider

Lifestyle
Guarding Against Prescription Drug Side Effects
Be Certain that You Are Not Anemic
Keep Blood Pressure in the Low Normal Range

Lifestyle
Taking steps to improve one's overall health is highly recommended to help prevent or minimize age-associated mental impairment. For example, exercising regularly; not smoking; and monitoring blood cholesterol levels can reduce the risk of stroke and heart disease and keep arteries open, supplying the brain with essential oxygen and nutrients. Regular exercise improves some mental abilities by an average of 20-30%. Abstaining from alcohol or drug use, or minimizing it, can also help preserve mental function. Because most persons tend to eat less food as they age, the use of low-fat, nutrient-rich food is recommended. This type of diet will help prevent nutrient deficiencies, which can impair mental function as a result of physical illnesses. Eating large quantities of high - antioxidant -containing fruits, especially berries (blueberries), may significantly provide protection from senility and many other age-related conditions. Mental exercise is another crucial lifestyle component. Forcing the memorization of dates, lists, and telephone numbers can help keep your mind sharp as you age. Engaging in activities that challenge acuity can also provide an "exercise" effect for your brain.


Guarding Against Prescription Drug Side Effects
Adverse side effects can result from either too high or too low doses of medications; unusual reactions to medications; or combinations of medications. It is especially common in the older population for individuals to be taking many different medications prescribed by different doctors, in addition to over-the-counter supplements. Be certain that your primary physician is aware of all prescription and nonprescription medications that you take.


Be Certain that You Are Not Anemic
A large number of aging people are anemic. Their physicians often fail to treat this condition because anemia is so common. Anemia represents a deficiency in the oxygen-carrying capacity of the blood. Blood should be tested annually. If there is any indication of even borderline anemia, seek medical assistance. For complete information about anemia, refer to the Anemia protocol.


Keep Blood Pressure in the Low Normal Range
A 30-year study of male twins showed that elevated blood pressure in mid-life predisposed men to accelerated brain aging and an increased risk of stroke later in life. Men with even mildly elevated blood pressure 25 years before showed smaller brain volumes and more strokes compared to their twin brothers who did not have the elevation in blood pressure. This study in the journal Stroke emphasized the importance of aggressively treating elevated blood pressure even when it is not grossly abnormal (DeCarli et al. 1999). Refer to the Hypertension protocol in this book for information about natural methods of controlling blood pressure.

The brain is the center of personal identity that makes us uniquely human. Decline in brain function is the greatest fear most persons have when thinking about aging.

Age-associated mental impairment can range in severity from forgetfulness to senility to dementia. Age-associated mental impairment can be caused by a wide variety of specific disease processes, many of which are treatable. It can also result from normal brain aging. Whatever its form or cause, age-associated cognitive impairment does not need to be accepted as an inevitable consequence of growing older.

Behavioral modification such as participating in increased physical and mental activity and following a healthy diet can improve mental function both directly and indirectly by enhancing overall health.

Age-associated mental impairment can be treated safely and effectively with memory-enhancing nutrients, hormones, and drugs. These therapies improve cerebral circulation; boost brain cell metabolism; stabilize brain cell membranes; increase acetylcholine; provide structural building blocks to neurons; synchronize brain cell interaction; restore youthful hormone balance; suppress free radicals; and reduce chronic inflammatory processes.

The benefit of taking several different types of agents that protect and enhance neurological function is that these same agents can also prevent age-associated diseases from manifesting in other parts of the body. Nutrients such as coenzyme Q10, acetyl-L-carnitine, and ginkgo, along with hormones such as DHEA, melatonin, and testosterone, can provide dramatic systemic anti-aging effects. A massive body of published scientific research indicates that one can take steps to boost cognitive function today, while simultaneously reducing the risk of Alzheimer's disease, stroke, and other degenerative brain diseases.

There is currently much debate as to whether mild cognitive decline or memory problems are a risk factor for developing more serious neurological disease, such as dementia or Alzheimer's disease. Some studies indicate that a significant percentage of elderly people complaining of mild cognitive impairment will go on to develop Alzheimer's disease. Clinical studies have been conducted in elderly people to see if the decline in cognitive function can be slowed and Alzheimer's disease can be postponed or prevented (Hanninen et al 1997; Richards et al. 1999; Grober et al. 2000; Collie et al. 2001; Goldman et al. 2001a; Goldstein et al. 2001; Petersen et al. 2001).

Perhaps the most important research paper published on age-associated memory impairment stated that memory decline is not a normal feature of aging. What the researchers found was that in persons with mild memory impairment, memory loss tended to progress, whereas persons who were healthy did not experience memory impairment as they aged (Goldman et al. 2001b).

If you have a neurological disorder such as cerebral vascular disease (stroke), Alzheimer's disease, Parkinson's disease, etc., refer to the in-depth protocols in this book that provide innovative treatment options that are often overlooked by conventional physicians.

The following are dietary supplements available in the United States that may benefit persons who have age-associated mental impairment:

Cognitex is a multi-ingredient formula providing nutrients such as vinpocetine, phosphatidylserine, glyceryl phosphorylcholine (GPC), and others discussed in this protocol. Three to six capsules of Cognitex daily are suggested.
Essential fatty acids such as DHA and EPA are found in Super EPA/DHA with Sesame Lignans. The recommended dose is two softgels twice daily with meals.
Ginkgo biloba extract, 120 mg daily.
Acetyl-L-carnitine arginate, three to four capsules daily.
Coenzyme Q10, 100-300 mg daily.
Lipoic Acid, 150-300 mg daily.
Life Extension Mix provides broad-spectrum, high-potency antioxidants, vitamins, and minerals. A suggested dose is three tablets, three times a day.
DHEA, 25-50 mg daily. Refer to the DHEA Replacement Therapy protocol before initiating DHEA or pregnenolone replacement.
Melatonin, 300 mcg to 3 mg nightly, a half hour before bedtime.
Phosphatidylserine (PS), 100-300 mg daily.
Vitamin B12 (preferably in the form of methylcobalamin), 1-40 mg daily.
Drugs and hormones requiring a prescription or that may be obtained from offshore pharmacies are:
Testosterone replacement, often indicated in aging males. Refer to the Male Hormone Modulation protocol in this book for complete details.
Estrogen replacement, often indicated in aging females. Increased risk of certain cancers and cardiovascular disease are of concern. Refer to the Female Hormone Replacement protocol for alternatives to estrogen drugs.
One or a combination of the following drugs may be considered:

Piracetam, 2400-4800 mg daily.
Centrophenoxine, 250-1000 mg daily.
Hydergine, 5-20 mg daily.
Deprenyl, one 5-mg tablet, two times weekly.
Nimotop (nimodipine), 30 mg, three times daily.
Chronic inflammation inflicts devastating effects, particularly as humans grow older. The pathological consequences of inflammation are fully documented in the medical literature. For example, in Alzheimer's disease, an inflammatory cascade is involved in many of the destructive processes observed in the neurons of patients, including the formation of toxic beta-amyloid. As this toxic inflammatory process continues, the loss of functioning neurons is accelerated, first resulting in mild cognitive impairment. Many scientists believe that unchecked inflammation is an underlying culprit in the development of Alzheimer's disease.

Because chronic inflammation is so injurious to brain cells, aggressive steps should be taken to suppress the inflammatory cascade. Some of the supplements recommended in this protocol, such as Super EPA/DHA w/Sesame Lignans, ginkgo, DHEA, and Life Extension Mix, can significantly reduce chronic inflammatory processes. For more information about drugs and additional therapies that are available to suppress dangerous inflammatory components in blood, please refer to the Inflammation (Chronic) protocol in this book.

As you have learned from this protocol, there are multiple diverse factors involved in the development of cognitive impairment and senility. Therefore, the emphasis should be on incorporating as many supplements, hormones, and drugs as are feasible to guard against the mechanisms involved in neuro-degeneration. For example, while supplements that increase acetylcholine (such as GPC) have become popular agents to improve short-term memory, they do not suppress a chronic inflammatory state nor do they appreciably boost brain cell energy metabolism.

Therefore, to optimally protect your brain from the numerous insults incurred as a result of normal aging and environmental toxins, a multimodal approach is needed that includes the proper dose of the nutrients, hormones, and drugs discussed in this protocol.

For More Information

Contact the National Institute on Aging, (800) 222-2225; the Alzheimer's Association, (800) 272-3900; and the National Institute of Neurological Disorders and Stroke, (800) 352-9424.

Product Availability

Cognitex, Super EPA/DHA w/Sesame Lignans, ginkgo biloba extract, vinpocetine, acetyl-L-carnitine arginate, coenzyme Q10, R-dihydro-lipoic acid, Life Extension Mix (containing essential vitamins and minerals), DHEA, melatonin, methylcobalamin (vitamin B12), and phosphatidylserine are available by telephoning (800) 544-4440 or by ordering online. Piracetam, high-dose Hydergine, and Centrophenoxine are available from overseas companies. A list of these companies can be obtained by calling (800) 226-2370. Testosterone patches, gels, or creams; estrogen drugs; and Hydergine, deprenyl, and nimodipine are available in the United States only by prescription.








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[SWALE]

Nice.

[Recless]

Interesting...My Dr. opted to put me on a low dose of Carbidopa-Levopa instead to increase low dopamine and low libido in spite of normal thyroid, and sex hormones. He said that he has tried Seleginine in the past on numerous patients and people don't respond too well to it...he said they felt sort of "numb" as if on antidepressants. This may be explained by the fact that Seleginine is reported to cause a notable increase in Serotonin in addition to dopamine.

[HeadDoc]

let us know how this turns out.

[chap]

I've played with it a little bit here and there,

never thought it did anything for me when I was on other things like test,

but thought it has a very slight libido improvement when I wasn't taking anything else with it,

but I also felt that kind of "numb" thing you are talking about, almost a bit of a spacey feeling at times, hard to put a finger on it, but it made it so I only used it sporadically,

I still have a couple boxes sitting around that I will probably take 1/4 of a tab once every few months when I feel like experimenting, I still wonder about the theoretical antiaging benefits and wonder if I should get on it as a long term thing, but I prefer to try to stay as natural as possible especially when it comes to brain chemicals

[Recless]

Quick update fellas...I have been on the L-Dopa for about 2 weeks and libido is up considerably! I am taking a low dose of (10mg/100mg) once in the afternoon. My overall sense of well being has has noticably improved as well as has my concentration and motivation, which was also one of the goals my Dr. and I hoped for with this treatment. He also does not think that I will desensitize myself to dopamine with this low a dose, even long term. I'll keep you guys posted.

[hardasnails1973]

Shippen puts all people on it and 90% saids it does shit.

[gettingold]

WHat supplement increases dopamine?

[Recless]

Originally Posted by hardasnails1973

Shippen puts all people on it and 90% saids it does shit.

HAN - Are you referring to Selegiline or L-Dopa? I haven't heard of any Shippen patients using Levdopa...

[gettingold]

I can't speak to what HAN meant but Selegiline is one of Dr. Shippen's main drugs

[Recless]

Originally Posted by gettingold

WHat supplement increases dopamine?

Phenylalanine is one but I would be careful if you have adrenal problems, because it will also raise norepinephrine which you don't want. Tyrosine is another, but again it can raise norepinephrine (and epinephrine). Both of these are precursors to dopamine. The sequence looks like this:

Phenylalanine -> Tyrosine -> Dopa -> Dopamine -> Norepinephrine

[gettingold]

Recless do you know if L-dopa raises norepinepherine?

[Recless]

Another quick update for those interested...My Dr. is switching me from Levodopa to Cabergoline. Although I did see an improvement with the Levodopa, it was not as substantial as we had hoped for. Based on recent labs it appears that my dopamine is still very low. My Dr. thinks that the dopamine it is producing are not lasting long or not enough of it is reaching my brain. I will report back on the Cabergoline. We are also trying to raise my estradiol which is also very low right now and contributing to my libido problems.

[thenxtgrt1]

Originally Posted by Recless

Another quick update for those interested...My Dr. is switching me from Levodopa to Cabergoline. Although I did see an improvement with the Levodopa, it was not as substantial as we had hoped for. Based on recent labs it appears that my dopamine is still very low. My Dr. thinks that the dopamine it is producing are not lasting long or not enough of it is reaching my brain. I will report back on the Cabergoline. We are also trying to raise my estradiol which is also very low right now and contributing to my libido problems.

I've used caber sporadically. I will say the results have been positive. It's nothing I would ever use long term. But one day I will attempt to take it for a couple of weeks straight with a set regimen.