The effects of omega-3 fatty acids monotherapy in Alzheimer's disease and mild cognitive impairment:

In my last post, I suggested that despite the findings of one study, it was still a good idea to supplement omega-3 fatty acids in the diet. Here is one study supporting my argument.

Forty-six seniors with mild to moderate Alzheimer's disease were given either a dose of omega-3's of 1.8 grams per day (roughly equivalent to what was provided in the previously mentioned study) or placebo. A 24-week, randomized, double-blind placebo-controlled study was carried out to test the feasibility of using omega-3 polyunsaturated fatty acids (PUFAs) monotherapy in people with cognitive impairment and to explore its effects on cognitive function and general clinical condition in these participants. Seventy-six participants completed the study. Those who received the omega-3's showed better improvement on a clinician-based assessment of symptoms. The change was more significant in those individuals with mild cognitive impairment than it was in those diagnosed with Alzheimer's disease.

The changes were more significant, also, in persons with higher concentrations of eicosapentaenoic acid (EPA) in their red blood cells.

And, as I suggested, study design is an important determinant of outcome. In the words of the researchers, "Further studies should be considered with a larger-sample size, diet registration, higher dosages, comparisons between different combinations of PUFAs, and greater homogeneity of participants, especially those with mild Alzheimer's disease and mild cognitive impairment."

I am excited to see what studies like this teach us about minimizing the devastating effects of diseases of aging, such as dementia and Alzheimer's disease!

Chiu CC, Su KP, Cheng TC, Liu HC, Chang CJ, Dewey ME, Stewart R, Huang SY. The effects of omega-3 fatty acids monotherapy in Alzheimer's disease and mild cognitive impairment: a preliminary randomized double-blind placebo-controlled study. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Aug 1;32(6):1538-44. Epub 2008 May 25.

Effect of fish-oil supplementation on mental well-being in older subjects: a randomized, double-blind, placebo-controlled trial.

We hear all the time that fish oil is good for mood. So why did this study here not come to that conclusion?

302 seniors (independently living) were divided into 3 groups. The first group was dosed 1800 daily milligrams of EPA and DHA, the second group 400 milligrams, and the third group received placebo capsules. Before being given the capsules, and 13 and 26 weeks into the study, plasma concentrations of EPA and DHA as well as responses to several psychological tests were measured. Even though the fish oil significantly increased EPA and DHA concentration in the two dosed groups (by 238% in the high dose and 51% in the low dose), responses to the questionnaires were not significantly different. Why is that? There are probably several reasons.

1. Brain function is about a lot more than just omega-3 balance. Independently living seniors are likely to be eating an overall diet that is deficient in several nutrients. It would have been interesting to see a baseline blood test of other nutrient levels to see if overall nutritional status was correlated with test scores and EPA/DHA response.
2. The background diet of these seniors was not measured, or if it was, it was not reported. If, which is common because of convenience, the group as a whole was eating a lot of pre-prepared and packaged food, the ratio of pro-inflammatory oils to dietary omega-3 content may affect the outcome of the study.

It doesn't mean that just because there was not a mood-based response to these oils that they weren't beneficial. If levels of omega-3's increased dramatically, they most certainly were reducing cardiovascular risk, preventing the development of dementia and Alzheimer's, and improving bone health, to mention a few.

I just wish these researchers would understand the importance of controlling diet in any study that investigates the usefulness of an isolated supplement. Not only will it provide more significant results, it will keep people from mistakenly assuming that a certain nutrient is not of benefit when it actually is.

van de Rest O, Geleijnse JM, Kok FJ, van Staveren WA, Hoefnagels WH, Beekman AT, de Groot LC. Effect of fish-oil supplementation on mental well-being in older subjects: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2008 Sep;88(3):706-13.

What happens in your brain when you have bipolar disorder

I love studies like this. They help substantiate that diagnoses such as bipolar disorder are not just "behavioral problems." They come with true biochemical imbalances, that sometimes even affect the tissue structure of the brain. Hopefully, the more studies like this are done, the less people with bipolar disorder will be looked down upon by society, and will be able to get the care they need that truly corrects these imbalances.

In this study, the fatty acid composition of the orbitofrontal cortex was studied in 10 patients with bipolar disorder. Compared to 19 cortices in individuals who did not have bipolar disorder. (This was performed in post-mortem, or after all the patients had died.)

Those individuals who had had bipolar disorder had higher concentrations of arachidonic acid and lower concentrations of docosahexaenoic acid (DHA) than those who had not. In both populations, there was also a trend toward higher arachidonic acid concentration and lower DHA concentration that was related to the degree of alcohol consumption.

A little visit over to Wikipedia gave me this information about the orbitofrontal cortex: Destruction...typically leads to a pattern of disinhibited behaviour. Examples include swearing excessively, hypersexuality, poor social interaction, compulsive gambling, excessive alcohol / smoking / drug use, and poor empathising ability. Disinhibited behaviour by patients with some forms of frontotemporal dementia is thought to be caused by degeneration of the OFC[8]. Patients with damage to the OFC tend to make rash decisions, and typically manage their finances poorly.

Sometimes it's easy to make judgments about a person's behavior and assume the person can just change them if they want to. It's reality that sometimes the problem is truly biological and that changing the nutritional status and/or the biochemistry of the brain is what is needed in order to help change behaviors.

McNamara RK, Jandacek R, Rider T, Tso P, Stanford KE, Hahn CG, Richtand NM. Deficits in docosahexaenoic acid and associated elevations in the metabolism of arachidonic acid and saturated fatty acids in the postmortem orbitofrontal cortex of patients with bipolar disorder. Psychiatry Res. 2008 Sep 30;160(3):285-99. Epub 2008 Aug 20.

Omega-3's for schizophrenia

DHA is commonly the omega-3 of the fish oils that gets the most attention for use in mental health conditions. However, EPA is gaining quite a reputation of its own. In this study, 24 patients presenting with their first episode of psychosis were treated with EPA for 12 weeks. Just before and at the end of this interval, brain scans were done to look for changes. Increases in glutathione and decreases in negative symptoms were observed as a result of EPA treatment.

Glutathione is a chemical that helps to prevent cell death, so its increase means EPA helps to preserve brain tissue. Because glutathione is not something that is easily administed via diet or supplementation, it's good to know there are other avenues for increasing its concentrations in populations at risk for greater rates of cell death, such as people with schizophrenia.

Berger GE, Wood SJ, Wellard RM, Proffitt TM, McConchie M, Amminger GP, Jackson GD, Velakoulis D, Pantelis C, McGorry PD. Ethyl-eicosapentaenoic acid in first-episode psychosis. A 1H-MRS study. Neuropsychopharmacology. 2008 Sep;33(10):2467-73. Epub 2008 Jan 16.

Why you can't just take a pill to feel better

Ohhh...I hate to say it, but we've become so lazy as a society. Evidence abounds that food, activity, stress management, and sleep choices can significantly affect overall health. But if given the option to try these or pay money for a pill or a medical procedure, the average American will tend to opt for the more passive option. Here's why those who make that choice may be selling themselves short.

Both omega-3 fatty acids and exercise have been found to improve brain function and keep brain tissue young.

A group of researchers is reporting that when the two are combined, compounds common in healthy, regenerating brain tissue (brain derived neurotrophic factor, or BDNF, for example) are higher than when only one of those options is applied. It seems as though the two play off of each other and each makes the other more effective.

Sorry, guys, there's no such thing as a way out of exercise and all the great things it does for you! :)

Wu A, Ying Z, Gomez-Pinilla F. Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition. Neuroscience. 2008 Aug 26;155(3):751-9.

A natural antipsychotic?

l-Stepholidine is a chemical derived from the Chinese herb Stephania. Since it had been found to have dopamine activity similar to that seen in atypical antipsychotics, it was tested and compared to the activity of haloperidol (Haldol) and clozapine (Clozaril). Scientists predicted its activity would more closely resemble clozapine. Indeed, when tested, it did mimic clozapine. The one downside researchers did report was that it was eliminated fairly rapidly from the body, which would make it challenging to use as a long-term therapeutic agent for treating schizophrenia.

What is stepholidine? It is a naturally occurring chemical, extracted from Stephania intermedia, a Chinese herb. I like to find pictures of herbs to share in this blog, but unfortunately, even Google can't pull anything up on this one.

I think this is exciting news, but being that this is very new information, I certainly am not recommending that anyone stop using a prescribed antipsychotic and head for Chinatown! I do promise, if anything new comes up, I'll be sure to share it in this blog along with references.

Natesan S, Reckless GE, Barlow KB, Odontiadis J, Nobrega JN, Baker GB, George SR, Mamo D, Kapur S. The antipsychotic potential of l-stepholidine--a naturally occurring dopamine receptor D1 agonist and D2 antagonist. Psychopharmacology (Berl). 2008 Aug;199(2):275-89.

When it takes more than a minute to describe how many medications you're taking...time to take a closer look.

Yesterday I was lunching with a dear friend, who mentioned that one of HIS friends has started to have problems with diabetes. I knew this friend also has Alzheimer's disease, so, knowing that many brain and nervous system-targeted medications can provoke insulin resistance and diabetes, I started asking questions about this person's medications.

We called the friend we were discussing for a complete list. Sure enough, in the battery of medications he had been prescribed...was valproic acid, or Depakote. Depakote is well documented to promote the development of metabolic syndrome--a cluster of problems including hypertension, insulin resistance, diabetes, and high cholesterol. Much of the research in this area has focused on women, because polycystic ovary syndrome, a feminine variant of metabolic syndrome, is also correlated with Depakote use. If you're looking for research on the effects of Depakote in men, it's there, it's just a little harder to find.

New research is suggesting that there is a link between diabetes and Alzheimer's disease. Some researchers even call it diabetes of the brain, and there is some evidence to suggest that diabetes medications such as metformin can help delay the progression of Alzheimer's syndrome.

So here we have a guy who has been prescribed a seizure medication, which has likely provoked his problems with diabetes, which is likely worsening his Alzheimer's disease...and what do you know? It seems as though now that he is on galantamine (Reminyl) for his Alzheimer's disease, he's started noticing tremors. I'd bet money on the possibility that the seizure meds are adjusted upward as a result.

So you can see where I'm going. Not only does this keep this poor guy's physicians busy, it pads the pockets of more than one pharmaceutical company, in progressively more expensive chunks.

My friend asked me what I would do? Well, I must qualify that I am not a prescribing medical doctor. I am a registered dietitian who studies the brain and nervous system. But this is where I'd go.

1. Based on the evidence that seizure disorders respond well to omega-3 fatty acids, I'd up those to a DHA equivalent of 1000 mg per day.
2. To help those omega-3's be most effective, I'd teach this person my "S" and "C" rule (avoid, as much as possible, all fats and oils beginning with the letters "S" and "C"...canola being the only exception). I know my friend and his friend eat out quite a bit and it likely is a significant source of these oils.
3. If you reduce the seizure and tremor activity, you reduce the need for seizure medication, and minimizing medications is always very important.
4. I would consider an alternative seizure medication with less potential for disrupting hormone balance. The one that I have seen repeatedly and successfully used in women to achieve this is lamotrigine (Lamictal). Of course, there may be a reason we do not know of that this would not be appropriate, but if this has not been considered it's certainly worth a try.
5. Less Depakote (or potentially no Depakote) potentially also means less insulin resistance, which provides the possibility that the Alzheimer's medication could be reduced. Again, less meds....fewer side effects.
6. Finally, acetyl l-carnitine has been shown to effectively reduce symptoms of diabetes as well as Alzheimer's disease. It also improves cholesterol profiles. And...it has repeatedly and specifically been found to effectively counter the negative side effects of Depakote. I have seen this cited so often recently I can't understand why it is not automatic for any physician prescribing Depakote to simultaneously recommend carnitine.

This trend, of treating one symptom, letting side effects develop, then treating them with other meds that create other side effects, which eventually build vicious cycles of ever-increasing doses of medications...in recent years...has spiraled out of control. The field of nutritional psychiatry is just out of the starting gate. But I'm hooked on its potential. Hopefully in this case, and for others who find this blog, we can help back our friends out of these pharmaceutical corners, save them some money, and improve their overall quality of life.



Luef G, Abraham I, Trinka E, Alge A, Windisch J, Daxenbichler G, Unterberger I, Seppi K, Lechleitner M, Kramer G, Bauer G. Hyperandrogenism, postprandial hyperinsulinism and the risk of PCOS in a cross sectional study of women with epilepsy treated with valproate. Epilepsy Res 2002 Jan;48(1-2):91-102.

Tan H, Orbak Z, Kantarci M, Kocak N, Karaca L. Valproate-induced insulin resistance in prepubertal girls with epilepsy. J Pediatr Endocrinol Metab 2005 Oct;18(10):985-9.

Aydin K, Serdaroglu A, Okuyaz C, Bideci A, Gucuyener K. Serum insulin, leptin, and neuropeptide y levels in epileptic children treated with valproate. J Child Neurol 2005 Oct;20(10):848-51.

Pylvanen V, Pakarinen A,Kniop M, Isojarvi J. Insulin-related metabolic changes during treatment with valproate in patients with epilepsy. Epilepsy Behav 2006 May;8(3):643-8.

Isojarvi JI, Laatikainen TJ, Pakarinen AJ, Juntunen KT, Myllyla VV. Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med 1993 Nov 4;329(19):1383-8.

Rasgon NL, Reynolds MF, Elman S, Saad M, Frye MA, Bauer M, Altshuler LL. Longitudinal evaluation of reproductive function in women treated for bipolar disorder. J Affect Disord 2005 Dec;89(1-3):217-25.

Roste LS, Tauboll E, Morkrid L, Bjornenak T, Saetre ER, Morland T, Gjerstad L. Antiepileptic drugs alter reproductive endocrine hormones in men with epilepsy.  Eur J Neurol. 2005 Feb;12(2):118-24.

Pylvanen V, Pakarinen A, Knip M, Isojarvi J. Characterization of insulin secretion in Valproate-treated patients with epilepsy. Epilepsia 2006 Sep;47(9):1460-4. Neurology. 2008 Sep 2;71(10):750-7.

Beeri MS, Schmeidler J, Silverman JM, Gandy S, Wysocki M, Hannigan CM, Purohit DP, Lesser G, Grossman HT, Haroutunian V. Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology. Prescrire Int. 2007 Oct;16(91):197-8.

McCain KR, Sawyer TS, Spiller HA. Evaluation of centrally acting cholinesterase inhibitor exposures in adults. Ann Pharmacother. 2007 Oct;41(10):1632-7.

López-Pousa S, Garre-Olmo J, Vilalta-Franch J. [Galanthamine versus donepezil in the treatment of Alzheimer's disease] Rev Neurol. 2007 Jun 1-15;44(11):677-84.

Schrauwen E, Ghaemi SN. Galantamine treatment of cognitive impairment in bipolar disorder: four cases. Bipolar Disord. 2006 Apr;8(2):196-9.

Aarsland D, Hutchinson M, Larsen JP. Cognitive, psychiatric and motor response to galantamine in Parkinson's disease with dementia. Int J Geriatr Psychiatry. 2003 Oct;18(10):937-41.

Isojarvie JI, Rattya J, Myllyla VV, Knip M, Ovine R, Pakarinen AJ, Tokay A, Tapaneinen JS. Valproate, lamotrigine, and insulin-mediated risks in women with epilepsy. Ann Neurol 1998 Apr;43(4):446-51.

Ribacoba-Montero R, Martinez-Faedo C, Diaz C, Salas Puig J. [Remission of polycystic ovary syndrome associated with valproic acid in an epileptic female]. Rev Neurol 2003 Apr 1-15;36(7):639-42.

Bruno G, Scaccianoce S, Bonamini M, Patacchioli FR, Cesarino F, Grassini P, Sorrentino E, Angelucci L, Lenzi GL. Acetyl-L-carnitine in Alzheimer disease: a short-term study on CSF neurotransmitters and neuropeptides. Alzheimer Dis Assoc Disord. 1995 Fall;9(3):128-31.

Thal LJ, Carta A, Clarke WR, Ferris SH, Friedland RP, Petersen RC, Pettegrew JW, Pfeiffer E, Raskind MA, Sano M, Tuszynski MH, Woolson RF. A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease. Neurology. 1996 Sep;47(3):705-11.

Sano M, Bell K, Cote L, Dooneief G, Lawton A, Legler L, Marder K, Naini A, Stern Y, Mayeux R. Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's disease. FASEB J. 1992 Dec;6(15):3379-86.