Dietary Supplements and Memory Potential to increase memory

Dietary Supplements and Memory Potential to increase memory capabilities in the aging population - Maria Skouroliakou, Ph. D. , Clinical Pharmacist, Lecturer of Harokopeio, University of Athens, Director of TPN Nutrition and Pharmacokinetics at IASO Hospital, Greece - Presentation created by: Tania Mitsinikos

Agenda • Basic concepts of neural signaling and memory • Memory and Age • Memory Enhancers – how they work – studies on effectiveness • Other areas that could have similar effects • Which then work best?

Agenda • Basic concepts of neural signaling and memory • Memory and Age • Memory Enhancers – how they work – studies on effectiveness • Other areas that could have similar effects • Which then works best?

Structure of the Neuron

Types of Receptors • Ionotropic receptor: allows various kinds of ions to rapidly cross the cell membrane into the neuron creating an electrical potential • Metabotropic receptors promotes the release of second messenger molecules and results in a number of biological changes in the cell.

Neural Signals: How do they work? • Neurotransmitter released and upon binding to ionotropic receptor, ions flood into the post-synaptic neuron, depolarizing the membrane, and proliferate the signal until it reaches its target where a response is initiated …but this doesn’t create memory…

Neural Signals to Create Memory • The neurotransmitter is released, and binding to a metabotropic receptor produces a second messenger which alters neuronal functioning • For example, activation of protein kinases cause prolonged changes in the neuron like the activation of certain genes and therefore protein synthesis resulting in formed memory

Agenda • Basic concepts of neural signaling and memory • Memory and Age • Memory Enhancers – how they work – studies on effectiveness • Other areas that could have similar effects • Which then works best?

Memory and Age: A gradual deterioration • Normal Aging leads to degenerative neural pathologies • 3 main changes in the brain – Neuronal changes (accumulation of nonessential substance, loss of myelin, and shrinkage) – Connections between neurons altered (reduced branching and reduced numbers, hence interfere with neurotransmitter availability) – Change cerebrovascular system leading to decreased blood flow and consequently volume

Agenda • Basic concepts of neural signaling and memory • Memory and Age • Memory Enhancers – how they work – studies on effectiveness • Other areas that could have similar effects • What then works best?

Dietary supplements: Potential Memory Enhancers • Phosphatidylserine (PS) • Choline – Phosphatidylcholine – Citicoline • • Piracetam Vinpocetine Acetyl-L-cartinine Antioxidants – Vitamin E – Vitamin C

Memory Enhancers: Theoretical Mechanisms Mc. Daniel, Mark A. et al. “Brain Specific Nutrients: A Memory Cure? ” Nutrition 2003: 957 -975

How these supplements work: A closer look

Phosphatidylserine (PS) • Naturally occurring phospholipid taken in through diet. • Especially important in phospholipid membranes of neurons – PS comprises a small percentage in biological membranes, but that small component may be critical in the membrane potential of neurons • Purchased without prescription

Phosphatidylserine (PS): Mechanism • Membrane and its receptors are critical for the neural signal to reach its target but with age, composition changes, and receptors are lost • Rigidity of membrane and message are not proliferated PS could reverse this, but how?

• Phosphatidylserine (PS): Protein kinase C Mechanism (PKC) is essential in secondary messaging in cell • PS and Ca 2+ ions activate PKC so the enzyme can be functional – PKC may then regulate neurotransmitters

Choline • Acetylcholine (ACh) is an important neurotransmitter and declines as individuals age, which severely impairs memory • Any source of choline could reverse ACh's declining levels like: – Phosphatidylcholine (PC) (main component lecithin) – Citicoline • Both can be purchased as nutritional supplements and some foods have been enhanced by adding lecithin

Choline: Mechanism • Choline is essential for • The number of neurons ACh production, so if it diminishes due to is supplemented to diet, age, so the remaining ACh levels rise and neurons may function potentially increase more effectively with memory capabilities more available ACh. Instead of gradual deterioration of neurons, choline supplements have the capabilities to help stop the destruction of neurons

Piracetam • A nootropic drug, first developed in 1967 • Sold as Nootropil and Pirroxil and one of the most widely know cognitive enhancing drugs • Not approved by Food and Drug Administration (FDA) • Available in Europe and Mexico

Piracetam: Mechanism • Enhances metabolism, improves neuronal efficiency, restores impaired neurotransmitters • Facilitates activity in several neurotransmission systems

Piracetam: Mechanism • May fight age related decrease in the number of N-methyl. D-aspartate (ionotropic receptor) and cholinergic receptors on neuronal membranes

Vinpocetine • Nootropic supplement derived from vincamine (extracted from periwinkle plant) • Introduced into clinical practice 20 years ago • Used to treat patients with loss of cerebral blood flow resulting in cerebral oxygen deficits

Vinpocetine: Mechanism • Increase blood flow • Improved blood flow in brain and increased prevents damage and/or transport and uptake death to neurons and of glucose to neurons prevents memory loss Could potentially increase ACh levels as well!

Acetyl-L-carnitine • Amino acid • Sold as “brain power” supplements in health food stores • Promotes synthesis and release of ACh • Provides energy for repair and maintenance of neurons

Acetyl-L-carnitine: Mechanism • Aids transport of substances across mitochondrial membranes and therefore assisting energy production • Increase PKC activity • Increase levels of neurotrophins • Neurotrophins guide differentiation and growth of nerves, maintain adult neurons, and are critical in repair of damage neurons. Needed to produce structural changes that are essential for permanent neurons • Protection for CNS synapses

Antioxidants • Aid in prevention of oxidative damage • Act as buffers • Vitamin E and C are antioxidants and have capabilities of memory enhancement

Antioxidants • Brain more vulnerable to oxidative stress due to immense amounts of O 2 being consumed • Oxidative stress causes damage to neurofilament proteins and induces death • By increasing antioxidant levels, it may slow down or stop the damaging effects of oxidation on neurons

Agenda • Basic concepts of neural signaling and memory • Memory and Age • Memory Enhancers – how they work – studies on effectiveness • Other areas that could have similar effects • What then works best?

Memory Enhancers: How effective are they? This all sounds like it could overcome a huge hurdle of declining memory as we age, but do these supplements live up to what they claim to fix?

Phosphatidylserine (PS): Studies • Effects on patients with moderate cognitive impairments: – several double-blind, placebo-controlled experiments in Italy (300 mg/day, 3 of 100 mg for 8 -24 weeks) – Conducted memory tests, before, after and during the study – Consistently and significantly increased total recall versus placebo but relatively modest results.

Phosphatidylserine (PS): Studies • Effects on normal aging adults (50 -75 yrs) with age related memory impairment – double-blind, placebo-controlled, 12 week study – 5 mnemonic memory tests, administered every 3 weeks – resulted in only moderate improvement based on these tests (improvements during first 6 weeks but no improvement after)

Phosphatidylserine: Studies • Details of study – double-blind, placebo-controlled, 8 -24 week study – 55 -88 y with moderate cognitive decline as determined through screening tests – 300 mg/day, 3 doses of 100 mg or placebo – Memory tests before, after and during treatment • Short lists of words (5 -15) were auditorily presented (1 word/sec) and auditorily recalled

Phosphatidylserine: Studies • Results – PS consistently improved total recall although uniformly modest • recall increases by 1 -2 words total • Placebo recall decreased by less than a word – No other signs of improved memory except for word recall

Choline: Studies • Phosphatidylcholine (PC): – Studied for treatment of Alzheimer’s disease – Uniformly negative results – No strong support that PC will prevent memory deterioration for patients with probably Alzheimer’s – Positive preliminary in the improvement of memory with memory problems due to aging

Choline: Studies • Citicoline: Details of study – double-blind, placebo-controlled of 42 days • 1000 mg/day treatment of 72 year olds (avg. ) – Patients had dementia-related decline rather than normal-age associated memory impairment (as determined by MMSE)

Choline: Studies • Citicoline: Results – Improved immediate and delayed prose recall relative to base line – Confirmed that choline levels increase • Consistent with idea that changes in brain metabolism related to acetylcholine levels and PC underlies mnemonic benefits èSafety: Some patients complained of insomnia, stomach distress, headache, rash, and cardiac anomalies

Piracetam: Studies • Details of Study – Initial double-blind, crossover study on patients with probably Alzheimer’s disease • 4. 8 g/day + lecithin for 3 months • tested memory with multiple-recall-trial procedure with same list of words – No significant findings but in patients with Alzheimer's type dementia the treatment with Piracetem and lecithin may substantially improve specific memory deficits – Other follow up studies failed to show positive results

Vinpocetine: Studies • Details of Study: – 3 months in duration • 10 mg, 3 times a day for 1 st 30 days • 15 mg/day for last 60 days • older adults with brain dysfunction (either circulatory problems or mild to moderate dementia-related brain disease

Vinpocetine: Studies • Results: – Showed improvement than placebo groups for tests of measuring attention, concentration, and memory. Size of improvement for reported scores was noticeable. – Increased scores on Mini-Mental Status Questionnaire but placebo showed no improvement – No improvement in patients with Alzheimer’s Disease

Acetyl-L-Carnitine • Details of Study: – Patients with probably Alzheimer’s • Results: – Showed less decline than placebo, but effects not reversed but not significant difference – In other large-scale, double-blind, placebocontrolled studies, there has been minimal or no benefits of acetyl-L-carnitine with patients diagnosed with probably Alzheimer’s – Another study showed a slow down in cognitive deterioration

Antioxidants: Studies • Details of Study: – Patients with brain pathology of moderate severity • Vitamin E in 2000 IU/day for 2 years • 85 patients with Alzheimer’s disease of moderate severity – Normal younger adults • 17 -27 year old college students • 10 times the recommended daily dose (vitamins C and E) • Cognitive assessment at 3, 6, and 9 months

Antioxidants: Studies • Results: – Alzheimer’s disease patients: • Vitamin E delayed time before required institutionalization and loss of daily skills • Overall slowed effects of mental illness in subjects – Normal young adults • No significant difference

Agenda • Basic concepts of neural signaling and memory • Memory and Age • Memory Enhancers – how they work – studies on effectiveness • Other areas that could have similar effects • Which then work best?

What else could help? • Docosahexaenoic Acid (DHA) is the principle polyunsaturated fatty acid in the nervous system. – Its formation slows as we age and hence doesn’t provide the necessary fatty acid to the neurons – Studies have shown that deficits in this fatty acid impairs neuronal functioning and hence cognitive abilities by compromising neuronal structure. – Enhancement through supplements of this fatty acid has potential to reverse these cognitive impairments

Agenda • Basic concepts of neural signaling and memory • Memory and Age • Memory Enhancers – how they work – studies on effectiveness • Other areas that could have similar effects • Which then works best?

Which then works best? Which one do you think works best? Maybe a combination or has one through these studies shown to be most effective?

Works Cited Campbell, Neil A. et al. “Biology 6 th Edition. ” Menlo Park, CA: Benjamin Cummings, 2003 Garrett, Reginald H. and Charles M. Grisham. “Biochemistry 3 rd Edition. ” Belmont, CA: Thomson, 2005 Mc. Daniel, Mark A. et al. “Brain Specific Nutrients: A Memory Cure? ” Nutrition 2003: 957 -975 Watson, James D. et al. “Molecular Biology of the Gene 5 th edition”. Glenview, IL: Benjamin Cummings, 2004

Thank You! QUESTIONS PLEASE