Galantamine, the plant of Odysseus, can quell obesity inflammation …

Odyssean Nutrition for Mind and Body
In new research, galantamine now appears to be able
to restructure our bodies as well as our minds.
By Will Block

Who are you, and where do you come from?
What is your city and who are your parents?
I am amazed that you drank this potion
And are not bewitched. No other man
Has ever resisted this drug once it’s past his lips. But you have
a mind that cannot be beguiled.
You must be Odysseus, the man of many wiles.

— Circe to Odysseus, The Odyssey, Book X (Trans. Stanley Lombardo)

Here’s to The Odyssey and its author Homer, without which and whom the prehistory of the Mediterranean world would undoubtedly have been lost to us. We know, from the singer of its tales, that Odysseus (the epic poem’s hero) is invariably the champion of memory and the enemy of forgetfulness. That is no surprise given what Homer set out to do: to recall what is worth recalling, and not to forget what is important. Less obvious is Odysseus’ role as a deliberate hesitater. How could this be a virtue? Contrary to the stale adage, he who hesitates before acting is not lost, if it is done in order to ponder and think through the precipitant situation before acting. Then all outcomes are improved, and brain triumphs over brawn.

Force Without Wisdom Falls of Its Own Weight

As you would expect from a hero/warrior, the man of “twists and turns” has not one unnecessary ounce of fat on his body, yet he nevertheless relies far more on his mind than on his muscles. He does not regard thinking and doing as a choice between an either/or proposition. As Horace wrote, “Vis consili expers Mole ruit sua.” (Force without wisdom falls of its own weight.)


For those who are contemplative, it is
common to wonder why others seem
to have wisdom without weight.



Circe reaches across time with her memory-destroying poisons, seeking a new Odysseus or the hero with a thousand faces to control.
So if Odysseus gave birth to a new thought/action paradigm, why cannot we, his cultural descendants, embrace the rule of the wisdom-tempered action archetype as well? In Book X, Odysseus withstands the mind-bending poison (an anticholinergic) of the sorceress Circe by hesitating first on his way to her camp and then eating the black bulb of the plant moly (as antidote), which contains galantamine, the natural acetylcholinesterase inhibitor. He thereby protects his mind (some say, “his sword of reason”) against the induced equivalent of Alzheimer’s disease and his body against transformation and enslavement as a pig or wolf as was Circe’s inclination.

In Service of Both Bodies and Minds

The glad tiding is that we may be able to serve both our bodies as well as our minds in keeping pace with Homeric homeostasis. In new research, an extract from the same plant ingested by Odysseus now appears to be able to restructure our bodies as well as our minds.1

Wisdom Without Weight

During the course of your day, do you ever stop to take a good look at people who seems to be defying the odds of growing obese with age? What is it that draws your attention? Is it the way they move—without any significant effort? Or how they fit into their clothing? Do you check out the tightness of their abdomen? Or observe the confidence of their personal bearing? Do you ever wonder, aside from the gift of a superior inherited metabolism, that there might be something that they do, that keeps them sleeker, more slender, and wiser with age?

Do you ever go a step further, and play detective by observing their behavior? When you encountered such a person (of which there seem to be fewer and fewer these days), say in a mall or other public place, do you ever follow them, at least with your eyes? To see how effortlessly they walk, to scan who they are with or who they meet, to observe how they interact, even for example with a clerk in a store? If in a gym, do you watch how they exercise? If in a restaurant, do you discern what they eat, and how fast or slow they do it? Do you take notice if they use supplements? You are not alone. For those who are contemplative, it is common to wonder why others seem to have wisdom without weight.

Galantamine Suppresses Excessive Inflammation

If you’ve followed the obesity epidemic—how could you fail to?—you may have noticed that there are secondary consequences and that among these are hyperinsulinemia, hyperglycemia, dyslipidemia, elevated blood pressure, and fatty liver. All of these are collectively subsumed as the metabolic syndrome and associated with the low-grade systemic inflammation that excess fat causes. As the authors of the new paper cited above have previously discovered, neural cholinergic signaling can help control inflammation.2 Indeed in this prior paper, the authors demonstrate that the cholinergic agent galantamine suppresses excessive pro-inflammatory cytokine release.

In their new study, the main objective was to examine the efficacy of galantamine, a clinically-approved natural material, for alleviating obesity-related inflammation and associated complications. Following 8 weeks on a high-fat diet, an inbred strain of laboratory mice were treated with either galantamine (4 mg/kg) or saline for 4 weeks in parallel with mice on a low-fat diet, which were “treated” with a salt solution.

Reduced Body Weight and Adiposity

It came as a surprise that obese mice treated with galantamine had significantly reduced body weight, food intake, abdominal adiposity, plasma cytokine and adipokine levels, along with significantly improved blood glucose, insulin resistance, and hepatic steatosis.


Obese mice treated with galantamine
had significantly reduced
body weight, food intake, and
abdominal adiposity.


In addition, galantamine significantly alleviated impaired insulin sensitivity and glucose intolerance. When taken together, these results indicate a previously unrecognized potential of galantamine in alleviating obesity, inflammation, and other obesity-related complications in mice. These findings are extremely exciting and will undoubtedly propel interest for studying the efficacy of galantamine in the context of human obesity and the metabolic syndrome.


Neural cholinergic signaling
can help control inflammation.


Among the findings for lab animals treated with galantamine:

  1. Galantamine reduced body weight and food intake and suppressed adipose tissue accumulation in high-fat diet-fed mice
  2. Galantamine altered systemic cytokine/adipokine levels in high-fat diet-fed mice
  3. Galantamine lowered fasting blood glucose and plasma insulin, alleviated insulin resistance, and decreased plasma cholesterol levels in high-fat diet-fed mice
  4. Galantamine suppressed fatty liver disease manifestation in high-fat diet-fed mice
  5. Galantamine lowered body weight, suppressed food intake, and alleviated impaired insulin sensitivity and glucose intolerance in high-fat diet-fed mice

In summary:

  • Mice with high-fat diet-induced obesity were found to have significantly lower inflammatory states, as indicated by decreased circulatory IL-6, MCP-1, leptin and resistin levels (all of which are inflammatory responses).
  • Obese mice had reduced body weight and abdominal adiposity, with the lessening of hyperglycemia, hyperinsulinemia, hypercholesterolemia, insulin resistance, and fatty liver.


Obese mice treated with galantamine
were shown to have significant
antiobesity effects


Another benefit from galantamine …

Galantamine May Combat
Sleep Deprivation-Induced Amyloid

An interesting recent study published online in Science indicates that lack of sleep increases the build-up of amyloid-beta (Aβ), and thus may worsen Alzheimer’s disease.1 Of all the physiological manifestations of this most common form of dementia, the accumulation of Aβ plaque in the brain is the most characteristic, followed by neurofibrillary tangles. This finding is among the first to associate lack of sleep with Alzheimer’s disease.

Using mice engineered to have a version of Alzheimer’s disease, researchers at Barnes-Jewish Hospital in St. Louis studied levels of Aβ that were affected by whether the animals were awake or asleep. Amyloid levels rose in their brains when the mice were awake, but fell when they slept. To make things worse, when the researchers prevented the mice from sleeping, amyloid rose even more so than when they were merely awake, according to Dr. David Holtzman of Barnes-Jewish Hospital, who was a principal researcher in the study. “Sleep deprivation markedly accelerated [Aβ] plaque formation,” Dr. Holzman said in an e-mail to reutershealth.com.2

Then the researchers injected orexin, a compound that regulates sleep, into the brains of the mice. The mice stayed awake longer, and Aβ levels rose, but when orexin was blocked, amyloid levels decreased. Orexin is used in the sleep disorder narcolepsy, a condition which causes excessive sleepiness. As per Dr. Holtzman, these findings suggest that drugs that target orexin may be useful to try as Alzheimer’s treatments. In addition, these findings also reinforce the necessity to treat sleep disorders—not only for the immediate problems that they cause—but due to the fact that they may have a long-term impact on brain health, said Dr. Holzman.

The dismal news is that there are few effective treatments for addressing Alzheimer’s, despite a great many years of research. Alzheimer’s remains a mind-kleptomaniac, stealing our most precious memories. There is currently no cure.

However, the acetylcholinesterase inhibitor galantamine has been found, along with its ability to agonize nicotinic acetylcholine receptors, to enhance sleep—galantamine has been found to have a positive effect on sleep disorders3 and has been found to help to maintain good sleep4—and based on this recent research, that may indeed be another feather in its cap to help control Alzheimer’s disease.

It is estimated by the Alzheimer’s Association that more than 35 million people globally will suffer from Alzheimer’s disease or other forms of dementia in 2010.

References

  1. Kang JE, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR, Fujiki N, Nishino S, Holtzman DM. Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science 2009 Nov 13;326(5955):1005-7.
  2. Steenhuysen J. Lack of sleep may play role in Alzheimer’s: study. Reuters Health Report, September 24, 2009.
  3. Anon. Galantamine (reminyl) in the treatment of severe Alzheimer’s disease]. Zh Nevrol Psikhiatr Im S S Korsakova 2009;109(7):57-61.
  4. Chankrachang S, Senanarong V, Poungvarin N, Phanthumchinda K, Tavichachart N, Praditsuwan R, Nidhinandana S. The effect of Galantamine on sleep quality in Thai Alzheimer’s disease patients. J Med Assoc Thai 2008 Sep;91(9):1343-9.

To Sleep . . . Perchance to Dream

Does galantamine promote dreaming? Sleep disorders are common in older people—and counting sheep rarely helps. One study has shown that people who have sleeping difficulties suffer from more health problems and die earlier than people who sleep well.1 Victims of Alzheimer’s disease are especially prone to sleeplessness and other sleep-related problems, such as restlessness and nightmares. These conditions tend to get worse as the disease progresses, and they take an increasing toll on the patient. They cause fatigue during the day, of course; they often exacerbate behavioral problems, such as aggression and incontinence; and they further erode the patient’s ability to function in the activities of daily living.

All of this naturally impacts the caregivers, whose own ability to get a good night’s sleep is often impaired. A sleepy, cranky caregiver is not what the doctor ordered. The myriad problems entailed in taking care of an Alzheimer’s patient, which can be overwhelming to begin with, are made that much worse by sleep deprivation—so much so that the decision to institutionalize the patient may, in sheer desperation, be accelerated. Thus the physical, emotional, and financial costs associated with sleep disorders can be great indeed.

Under such circumstances, it stands to reason that one would want to avoid anything that might aggravate your difficulties in sleeping through the night. Unfortunately, however, that very characteristic has been observed in clinical trials with one of the most widely prescribed anti-Alzheimer’s drugs, donepezil.2 On the other hand, there has been no evidence of sleep problems associated with rivastigmine, another widely prescribed drug for Alzheimer’s, or with galantamine.

American researchers recently analyzed the data from three previously published clinical trials on galantamine to determine whether sleep disturbances were more prevalent among those taking galantamine (16 or 24 mg/day) than among those taking placebo.2 The analysis took into account the effects of any additional medications the patients were taking (including those for sleep disorders) during the trial periods.

The results showed that galantamine was well tolerated in terms of sleep: it produced no more adverse events than placebo, with one exception: a higher incidence of mild nightmares at the 24-mg/day dosage (although the incidence of nightmares was very low in both groups). Overall, galantamine was judged not to be a significant problem in terms of sleep—and that’s a blessing, all things considered.

References

  1. Dew MA et al. Healthy older adults’ sleep predicts all-cause mortality at 4 to 19 years of follow-up. Psychosomatic Med 2003;65:63-73.
  2. Stahl SM, Markowitz JS, Papadopoulos G, Sadik K. Examination of nighttime sleep-related problems during double-blind, placebo-controlled trials of galantamine in patients with Alzheimer’s disease. Curr Res Med Opin 2004;20(4):517-24.

It is a natural progression that studies on the use of galantamine to alleviate inflammation and other obesity-associated complications need to be done in humans. There is already a body of evidence showing that galantamine may ward off the devastations of memory decline, or at least delay the degradations. Some scientists have even suggested that Alzheimer’s might be a type of diabetes.


Odysseus … asked to be young again,
or at least not old …


Do You Want to Wear the Face of a Hero?

Although you may not be able to achieve the status of an Odysseus, if the hero truly wears a thousand faces, one of these might be yours. From The Lost Books of The Odyssey:

Odysseus thought a little while (or possibly a long while—he was distantly aware of nights passing, greenery sprouting from oak trees and withering away, through all of which Athena’s grin was immovable) and asked to be young again, or at least not old, and to spend eternity making his way from a war indefinitely far in the past to an island indefinitely far in the future.3

May you be young again, avoid the ravages of war, reach your island of peace, and of course achieve prosperity. Based on this recent study, your choice could be galantamine.

References

  1. Satapathy SK, Ochani M, Dancho M, Hudson LK, Rosas-Ballina M, Valdes-Ferrer SI, Olofsson PS, Harris YT, Roth J, Chavan S, Tracey KJ, Pavlov VA. Galantamine alleviates obesity, inflammation and other obesity-associated complications in high-fat diet-fed mice. Mol Med 2011 Jul 1. doi: 10.2119/molmed.2011.00083. [Epub ahead of print]
  2. Pavlov VA, Parrish WR, Rosas-Ballina M, Ochani M, Puerta M, Ochani K, Chavan S, Al-Abed Y, Tracey KJ. Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway. Brain Behav Immun 2009 Jan;23(1):41-5.
  3. Mason Z. The lost books of the odyssey. New York: Farrar, Straus, and Giroux; 2007.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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