Help for Post-Stroke Cerebral Insufficiency

Dear Dr. Dean,

My husband suffers from short-term memory loss due to strokes in Jan 2006 and again in 2012. He converses with people easily, but cannot recall what was said later in the day. He is 74 years old. His health is good. He has high blood pressure controlled by meds. He sleeps well. He is about 35 pounds overweight. What are your recommendations? What Life Enhancement products would be helpful?

ROSANNE, Belemont, AZ

Dear Rosanne,

It sounds as if your husband is suffering from Mild Cognitive Impairment (MCI), resulting from ischemic injury from a stroke. Although there’s no “silver bullet,” and no guarantees from any treatment, I suggest a number of approaches that may provide some relief and improvement:

Vinpocetine

Vinpocetine is an extract of the periwinkle plant, developed as a cognitive enhancer in Hungary over 30 years ago. It acts to increase cerebral blood flow, reduce blood viscosity, and increase the utilization of glucose and oxygen in the brain. One of the earlier human studies on vinpocetine involved 42 patients with “chronic vascular senile cerebral dysfunction” (i.e., mild-to-moderate dementia caused by inadequate blood flow to and within the brain).1 After taking 10 mg of vinpocetine three times/day for one month, followed by two-months of 5 mg three times/day, researchers noted improved general cognition of the patients. They concluded that vinpocetine improves memory, learning, and speech and language skills in patients suffering from vascular dementia.

More recently, researchers in Portugal also demonstrated that vinpocetine protects against neuronal ischemic injury in humans;2 and in Russia, ischemic stroke patients treated with 10 mg of vinpocetine three times/day for three months fared better than the control group on a National Institute of Health standardized Stroke Scale.3 A recent review article concluded that, “Vinpocetine is widely used in Japan, Hungary, Germany, Poland and Russia for the treatment of cerebro-vascular-related pathologies. Clinical studies have indicated the efficacy and safety of Vinpocetine as a neuroprotective, nootropic and anti-convulsant agent.”4

Vinpocetine has no known adverse effects, and is effective in doses of 20–40 mg per day.

Acetyl-L-Carnitine (ALC)

ALC is important for energetics in the brain and other tissues. ALC transports fatty acids from the cell cytoplasm into the mitochondria where they play a critical role in the generation of adenosine tri-phosphate (ATP), the body’s universal energy molecule. A number of studies of the effect of ALC on patients suffering from cerebrovascular ischemia—including many who had suffered strokes—were performed in the early 1990s.5–9 These studies demonstrated ALC’s ability to improve cerebral blood flow and memory and reaction time in a variety of tests. In 2003, a meta-analysis of randomized double-blind studies of the effect of ALC on mild cognitive impairment and early Alzheimer’s was conducted.10 The results showed a significant benefit for ALC in both clinical scales and psychometric tests. The beneficial effects were evident by 3 months, and continued over time.

The dosages used in all of the studies ranged from 1.5–3.0 gm per day, with no adverse effects reported.

Ginkgo biloba Extract (GBE)

Ginkgo biloba has been used traditionally in Asia for its ability to normalize blood pressure, increase libido, and improve cognitive performance in normal adults as well as those suffering from cognitive impairment. GBE is considered a drug in Germany, where it is one of the most widely prescribed drugs. It is also very popular in France and the Netherlands. In 1992, a rigorous meta-analysis was published in the British Journal of Pharmacology in which the authors reviewed 40 trials of Ginkgo biloba extract in cerebral insufficiency.11 The study examined the effects of GBE on 12 symptoms of cerebral insufficiency. All but one of these 40 trials reported positive effects of GBE on these symptoms. The authors cautioned that it may take 4–6 weeks of treatment before improvement is noted. The most commonly used dose in the studies was 120 mg GBE daily. In the same year, a German double-blind study of 72 patients with cerebral insufficiency treated with GBE or placebo found a statistically significant improvement in short term memory after 6 weeks.12 The authors concluded that, “GBE improves mental performance.”

Two recent studies confirm the clinical improvement of patients with acute and chronic cerebral ischemia. The first, from Iran,13 and the second, from Russia.14 Both papers report significant improvement in patients suffering from acute or chronic cerebral insufficiency.

I recommend GBE doses of 240 mg per day.

DMAE

One of the first substances Life Enhancement carried is DMAE (dimethylaminoethanol). DMAE is not known (to my knowledge) to help with cerebral insufficiency, but it does act as a mild cerebral stimulant, helps to elevate mood, improve memory and learning, heighten intelligence, increase physical energy and—in laboratory animals—extend the life span. DMAE probably works by accelerating the brain’s synthesis and turnover of the neurotransmitter acetylcholine, which in turn plays a key role in maintaining mental ability as well as supporting healthy memory in aging adults. It has also been suggested that DMAE may work, in part, by inhibiting choline metabolism in peripheral tissues, causing free choline to accumulate in blood, enter the brain, and stimulate cholinergic receptors.15,16

In 1958, Dr. Leon Oettinger, Jr., reported that DMAE:17

• Accelerated mental processes

• Improved concentration

• Stopped early morning “fogginess”

• Relieved lassitude and mild depression

• Increased attention

• Improved IQ

Figure 1. Life-extending effects of DMAE in A/J mice. (Hochshcild, 1973).
LEM1409Fig274.gif
(click on thumbnail for full sized image)

Although most of the human studies done with DMAE were conducted in the 1950s and 60s, more recent animal studies appear to confirm these early reports.18,19 Additional benefits of DMAE include its ability to prevent and reduce the accumulation of lipofuscin (which causes “aging spots”) in the skin, heart, muscles, kidneys, nerves and brain,20 and to extend the mean and maximum lifespan of experimental animals (Fig. 1).21

I recommend 500 mg DMAE be taken each morning.

Methylene Blue (MB)

A substance with which I’ve recently become aware, which has dramatically improved the cognitive abilities of several of my patients, is methylene blue. Methylene blue is the first synthetic drug, and has a more than 120-year history of diverse applications, both in medical treatment and as a staining reagent. In the pre-antibiotic era, it was used as a urinary tract antiseptic. In recent years, it has been used as an antimalarial agent, and as a potential treatment of neurodegenerative disorders such as Alzheimer’s disease.22

Methylene blue attenuates the formations of amyloid plaques and neurofibrillary tangles in the brain (characteristic of Alzheimer’s disease), and partially repairs impairments in mitochondrial function and cellular metabolism.23 For this reason, it may also help with cerebral insufficiency. Methylene Blue also inhibits acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), which favorably affect the neurotransmitter system believed to be involved in Alzheimer’s.24

Methylene blue is inexpensive and available by prescription from some compounding pharmacies. I prescribe doses of 50 mg per day. Patients need to be warned in advance that it will turn their urine a striking, almost phosphorescent blue color. The only other side effect that has been reported to me is that patients’ memories improve and they begin to act “normal.”

Although each of these nutrients tends to be beneficial when used separately, I’ve found that they generally are synergistic—i.e., they complement each other.

Other substances that might be beneficial for your husband include Durk & Sandy’s high-potency EPA/DHA-containing Omega-3 formulas (for their anti-inflammatory, anti-coagulant effects), and their low-glycemic food formulas (to help with weight loss).

Please let me know how he does,

Ward Dean, MD

References

  1. Balestreri R, Fontana L, Astengo F. A double-blind placebo controlled evaluation of the safety and efficacy of vinpocetine in the treatment of patients with chronic vascular senile cerebral dysfunction. J Am Geriatr Soc. 1987;35:425-30.
  2. Santos MS, Duarte AI, Moreira PI, Oliveira CR. Synaptosomal response to oxidative stress: effect of vinpocetine. Free Radic Res. 2000;32:57-66.
  3. Feigin VL, Doronin BM, Popova TF, Gribatcheva EV, Tchervov DV. Vinpocetine treatment in acute ischaemic stroke: a pilot single-blind randomized clinical trial. Eur J Neurol. 2001; 8:81-5.
  4. Patyar S, Prakash A, Modi M, Medhi B. Role of Vinpocetine in cerebrovascular diseases. Pharmacologic Reports. 2011;63(3):618-28.
  5. Rosadini G, Marenco S, Nobili F, Novellone G, Rodriguez G. Acute effects of acetyl-L-carnitine on regional cerebral blood flow in patients with brain ischaemia. Int J Clin Pharmacol Res. 1990;10(1-2):123-8.
  6. Arrigo A, Casale R, Buonocore M, Ciano C. Effects of acetyl-L-carnitine on reaction times in patients with cerebrovascular insufficiency. Int J Clin Pharmacol Res. 1990;10(1-2):133-7.
  7. Postiglione A, Cicerano U, Soricelli A, De Chiara S, Gallotta G, Salvatore M, Mancini M.Cerebral blood flow in patients with chronic cerebrovascular disease: effect of acetyl L-carnitine. Int J Clin Pharmacol Res. 1990;10(1-2):129-32.
  8. Postiglione A, Soricelli A, Cicerano U, Mansi L, De Chiara S, Gallotta G, Schettini G, Salvatore M. Effect of acute administration of L-acetyl carnitine on cerebral blood flow in patients with chronic cerebral infarct. Pharmacol Res. 1991 Apr;23(3):241-6.
  9. Lino A, Boccia MM, Rusconi AC, Bellomonte L, Cocuroccia B. [Psycho-functional changes in attention and learning under the action of L-acetylcarnitine in 17 young subjects. A pilot study of its use in mental deterioration]. Clin Ter. 1992 Jun;140(6):569-73.
  10. Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer’s disease. Int Clin Psychopharmacol. 2003 Mar;18(2):61-71.
  11. Kleijnen J, Knipschild P. Ginkgo biloba for cerebral insufficiency. Br J Clin Pharmacol. Oct 1992; 34(4):352–8.
  12. Grässel E. [Effect of Ginkgo-biloba extract on mental performance. Double-blind study using computerized measurement conditions in patients with cerebral insufficiency]. [Article in German] Fortschr Med. 1992 Feb 20;110(5):73-6.
  13. Oskouei DS, Rikhtegar R, Hashemilar M, et al. The effect of Ginkgo biloba on functional outcome of patients with acute ischemic stroke: a double-blind, placebo-controlled, randomized clinical trial. J Stroke Cerebrovasc Dis. 2013 Nov;22(8):e557-63. doi: 10.1016/j.jstrokecerebrovasdis.2013.06.010. Epub 2013 Jul 18.
  14. Odinak MM, Kashin AV, Ememlin AIu, Lupanov IA. [Therapeutic correction of mild cognitive impairment in patients with chronic cerebral ischemia]. [Article in Russian] Zh Nevrol Psikhiatr Im S S Korsakova. 2013.
  15. Haubrich DR, Gerber NH, Pflueger AB. DEANOL affects choline metabolism in peripheral tissues of mice. Neuropsychopharmacol. J Neurochem. 1981;37:476-82.
  16. Millington WR, McCall AL, Wurtman RJ. DEANOL acetamidobenzoate inhibits the blood brain barrier transport of choline. Ann Neurol. 1978;4:302-6.
  17. Oettinger L. The use of Deanol in the treatment of disorders of behavior in children. J Pediat. 1958;53:761-5.
  18. Levin ED, Rose JE, Abood L. Effects of nicontinic dimethylaminoethyl esters on working memory performance of rats in the radial-arm maze. Pharmacol Biochem Behav. 1995 Jun-Jul:51(2-3):369-73.
  19. Malanga G1, Aguiar MB, Martinez HD, Puntarulo S. New insights on dimethylaminoethanol (DMAE) features as a free radical scavenger. Drug Metab Lett. 2012 Mar;6(1):54-9.
  20. Zs-Nagy I, Floyd RA. Electron spin resonance spectroscopic demonstration of the hydroxyl free radical scavenger properties of dimetheylaminoethaol in spin trapping experiments confirming the molecular basis for the biological effects of Centrophenoxine. Arch Gerontol Geriatr. 1984 Dec:3(4):297-310.
  21. Hochschild R. Effect of dimethylaminoethanol on the life span of senile male A/J mice. Exp Gerontol. 1973;8(4):185-91.
  22. Schirmer RH, Adler H, Pickhardt M, Mandelkow E. Lest we forget you—methylene blue … . Neurobiol Aging. 2011 Dec;32(12):2325.e7-16. doi: 10.1016/j.neurobiolaging.2010.12.012. Epub 2011 Feb 12.
  23. Oz M, Lorke DE, Petroianu GA. Methylene Blue and Alzheimer’s Disease. Biochem Pharmacol. 2009 Oct 15; 78(8):927-32.
  24. Petzer A, Harvey, BH, Petzer JP. The interactions of azure B, a metabolite of methylene blue, with acetylcholinesterase and butyrylcholinesterase. Toxicol Appl Pharmacol. 2014 Feb 1;274(3):488-93.

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