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What is a Liposome?

(lĭp′ə-sōm′, lī′pə-)

Not discernable with a light microscope, a nanoliposome can be seen under an electron microscope as a sphere. Just as a water balloon has a thin outer layer with a water-filled interior, a liposome likewise has a thin outer wall — similar to a membrane — made of a phospholipid bilayer and an interior containing a water-soluble material. First identified in the early 1960’s, liposomes have undergone extensive research, the aim being the optimization of encapsulation, stability, circulation time and targeted delivery of its cargo, which may be a drug or a nutrient to a specific site of action. Until recently, the use of liposomes as a carrier of nutriments was limited, the delivery of drugs being more the focus. Their versatility is now being realized in other domains.

A few companies are pioneering the benefits of this unique science. It has long been the case that absorption and bioavailability rates of oral dietary and nutritional tablets and capsules is low and unreliable. Now, the natural encapsulation of lipophilic and hydrophilic nutrients within a liposome has created an effective method of bypassing the destructive elements of the digestive system, allowing the encapsulated nutrient to be delivered directly to cells and tissues.

To make a suitable microscope image, the liposomes are frozen and then sliced into ridiculously thin layers. This “freeze fracturing” will open some, but not all, and you will be able to distinguish the intact spheres from the concave surfaces of the incised liposomes. If this arrangement fails to emerge, you most likely do not have liposomes. But most clinics and manufacturers do not own electron microscopes. So, how do you determine that you have liposomes? Mix your material with water. Solid globs of amorphous matter are not carrying anything inside them and are not liposomes. If this happens, the phosphatidylcholine (PC) content is either too low, of poor quality, or is non-existent. If what you think is a liposome appears to be floating in foam, you are stuck with a mere emulsion, not a liposome. The liquid around a liposome should be clear.

Liposomes do not form spontaneously, typically needing energy applied to a dispersion of PC in a polar solvent, such as water. Heat, agitation and the aqueous province of the human body afford the right conditions. Sonication of phospholipids in water does the same thing, but likely will form layers like those of an onion, with progressively smaller liposomes. The inclusion of ancillary lipids facilitates the preparation. Microscopic vesicles — nanoliposomes — of PC can trap desirable payloads and provide controlled release of various bioactive agents at the right place at the right time. Here, otherwise volatile, reactive or sensitive additives become stabilized. Liposomes are bioresponsive because they and cell membranes share a common constituent — the lipid bilayer. As liposomes and cell membranes sidle near each other, they become conjugated and meld into each other, allowing the liposomal cargo to be deposited in the cellular cytosol, where its ameliorative destiny can be fulfilled. Liposomes with target specificity offer the prospect of safe and effective therapy for challenging clinical uses.

Vitamin D & The Brain

Vitamin D DeficiencyVitamin D deficiency has hit an epidemic level. Not only are intakes devastatingly low, but also exposure to the sun has become increasingly limited for fear of contracting skin cancer. In his June 23, 1011, newsletter at Newsmax Health, Dr.Russell Blaylock educates his readers when he states that vitamin D3 is actually a hormone rather than a vitamin, and that a deficit of this compound may result in undesirable consequences in the brain, including depression.

Dr.Blaylock is a renowned neurosurgeon with a keen desire for people to take some control over their own health.  He implies that supplemental vitamin D3, “…lowers risk of infections, which would reduce the incidence of brain inflammation.”   He adds that research can place behavioral disorders in the lap of vitamin D deficiency, and  suggests that all of us get a vitamin D blood-level test to find out where we stand, noting that current accepted values are too low to be any benefit.   About the conditions, Dr. Blaylock says, “…depression, anxiety, panic attacks, obsessive-compulsive disorder, suicide risk, and even criminal behavior…can be traced to chronic brain inflammation.”  The good doctor would like to see blood vitamin D levels between 70 and 100 nanograms per milliliter.  That means that most of us need to take at least 2000 IU of vitamin D3 a day, with as much as 10,000 IU for severe deficiency.

The body needs cholesterol to make vitamin D from the sun’s ultra-violet radiation.  When the resulting chemical mix gets to the liver it becomes vitamin D3, the active form of the hormone, which the body uses to help maintain bone integrity, to increase neuromuscular function, and to modulate the immune system.  There has been considerable support over the past decade for the role of vitamin D in brain development and function.  It was noted by Kesby and colleagues at Australia’s Queensland Brain Institute that, “…this vitamin is actually a neuroactive steroid that acts on brain development, leading to alterations in brain neurochemistry and adult brain function.”  (Kesby. 2011)  Deficiencies have been related to depression, as well as to Parkinson’s disease and cognitive decline.

Of particular interest to American researchers at the U. of South Carolina is the relationship of vitamin D deficit to postpartum depression as one of the several mood disorders studied in 2010.  Using a moderate sample size at the outset, scientists found that low levels of vitamin D are associated with increased postpartum depression, as measured by evaluation on the Edinburgh Postpartum Depression Scale. (Murphy. 2010)  Even though larger studies are encouraged, the outcomes are likely to be the similar.

When the immune system abandons its competence because of nutritional deficit, inflammation ensues, often with a mighty wrath.  Such is the case with deficit of vitamin D in various maladies that include diabetes and multiple sclerosis, as well as depression.  Depression is a family affair characterized by feelings of hopelessness, despair, anxiety, irritability and restlessness.  Depression understandably accompanies degenerative disease, in part by the hopelessness is may engender.  If vitamin D is able to address depression, might it also be able to help get a handle on these conditions?   Whatever the cause of vitamin D deficiency, levels lower than 30 nanograms per milliliter have been associated with heart disease, type 2 diabetes, infectious diseases, autoimmune disorders, and neurological conditions. (Nimitphong. 2011)

References

MAIN ABSTRACT
Dr. Blaylock
Up Vitamin D3 for Your Brain
Thursday, June 23, 2011 10:11 AM

SUPPORTING ABSTRACTS
Mol Cell Endocrinol. 2011 Jun 1. [Epub ahead of print]
The effects of vitamin D on brain development and adult brain function.
Kesby JP, Eyles DW, Burne TH, McGrath JJ.

Source Queensland Brain Institute, University of Queensland, St. Lucia, Qld 4076, Australia.

J Am Psychiatr Nurses Assoc. 2010 May;16(3):170-7.
An exploratory study of postpartum depression and vitamin d.
Murphy PK, Mueller M, Hulsey TC, Ebeling MD, Wagner CL.

SourceMedical University of South Carolina, Charleston, SC, USA, [email protected]

Curr Opin Clin Nutr Metab Care. 2011 Jan;14(1):7-14.
Vitamin D, neurocognitive functioning and immunocompetence.
Nimitphong H, Holick MF.

SourceSection of Endocrinology, Diabetes, Nutrition, Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA.

Acta Psychiatr Scand. 2011 Apr 12. doi: 10.1111/j.1600-0447.2011.01705.x. [Epub ahead of print]
D’ for depression: any role for vitamin D?: ‘Food for Thought’ II.
Parker G, Brotchie H.

SourceSchool of Psychiatry, University of New South Wales, and Black Dog Institute, Randwick, Sydney, NSW, Australia.

Psychopharmacology (Berl). 2011 Jun;215(4):733-7. Epub 2011 Jan 29.
Exploring the relationship between vitamin D and basic personality traits.
Ubbenhorst A, Striebich S, Lang F, Lang UE.

SourceDepartment of Physiology, University of Tuebingen, Gmelinstr. 5, 72076, Tuebingen, Germany.

FASEB J. 2008 Apr;22(4):982-1001. Epub 2007 Dec 4.
Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction?
McCann JC, Ames BN.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Phthalate Exposure

colorful-car-toyPhthalates are endocrine disrupters, widely present in the environment and able to impede mental and motor development in children by causing changes in the nascent brain. These chemicals are found in many consumer products, from shower curtains to plastic toys to shampoo and hair spray. Their ubiquity has led scientists to look more closely into the risks associated with exposure to phthalates during pregnancy. What they found was sufficiently disconcerting to make you scrutinize the products you buy if you are pregnant or contemplating being so.

Dr. Robyn Whyatt, from Columbia University’s Mailman School of Public Health, reported in September, 2011, that prenatal exposure to metabolites of four different types of phthalates significantly increases the chances of physical and mental delay, indicating the potential for future problems with gross and fine motor coordination.  “Our results suggest that prenatal exposure to these phthalates adversely affects child mental, motor and behavioral development during the preschool years,” commented Dr. Whyatt, adding that, “The results add to a growing public health concern about the widespread use of phthalates in consumer products.”  (Whyatt.  2011)  Although the actual mechanisms by which phthalates wreak their malevolence are still being examined, their endocrine disruption has been specifically linked to thyroid hormone and testosterone production.  Partner to the study, Dr. Pam Factor-Litvak explained that, “The results are concerning since increasing exposures from the lowest 25% to the highest 25% among the women in our study was associated with a doubling or tripling in the odds of motor and/or behavioral problems in the children.”

If you’re a baby boomer, you associate plastic with the cheap imported toys of the 50’s and 60’s, stuff that would snap in an instant.  Plastics—plasticizers in the case of phthalates–actually are materials that make other materials easier to handle, more flexible and pliable, and less brittle.  They work best if their molecules are both polar and non-polar, where the former help the plasticizer be retained in the system, and the latter decrease the attraction force between molecules to maintain flexibility.  This is how hair spray works; it’s flexible.  Otherwise, you’d be wearing a transparent motorcycle helmet.

Of the more than five hundred plasticizers available, fewer than a hundred are commonly used, phthalate esters being predominant, especially in PVC.  The real name for the most often used of these chemicals is orthophthalates.  It’s necessary to know that phthalates are not limited to the manufacture of containers, which is a common thought.  They are also ingredients in cosmetics, shower curtains, teething rings and toys, primarily because they afford flexibility.  However, they have the contemptible distinction of mimicking female hormones, resulting in the feminization of boys.  It’s one thing to have swapped paternal inheritance for creeping momism as a social misfeasance, which is rectifiable, but this physical assault is unforgiveable.

There is more than one type of phthalate to which a fetus might respond, some being termed less dangerous than others.  This is equivalent to saying that a person who is legitimately allergic to tree nuts will succumb more slowly to one type of nut than another.  In both cases the outcome is undesirable.  Delay of ossification in the skeleton with resultant deformities, cleft palates, eye deformation, and decreased fetal weight are but a few of the other abnormalities offered by phthalate plasticizers.  These are dose-dependent anomalies, but determining how much is too much is subjective. (Saillenfait. 2009)  The limit for phthalate exposure is set at 5 mg/kg of body weight a day…in rats.  .  (Grande. 2006)  People are not likely to get anything close to that dose unless they eat the plastic.

To assuage any fears, know that the PETE, polyethylene terephthalate, used for peanut butter jars, bottled water and juices, and salad dressings is not chemically similar to the phthalates we address here.  Phthalates are additives, not plastics.  PETE (aka PET) is not an orthophthalate.  If the dangers come from prenatal exposure to phthalates, it pays for the new mom to read labels.  Since 2002, safe alternatives are available for the manufacture of plastic wraps, food containers, toys, PVC pipe, medical devices, and health and beauty aids.  Citric acid esters are one of them.  To find out if your product is safe, check the ingredients.  If there is no label, as perhaps with a teething ring, either call the maker or leave it on the shelf.

References

http://www.mailman.columbia.edu/news/prenatal-exposure-phthalates-linked-decreased-mental-and-motor-development-and-increased-behavior
Prenatal Exposure to Phthalates Linked to Decreased Mental and Motor Development and Increased Behavioral Problems at Age Three

Robin M. Whyatt, Xinhua Liu, Virginia A. Rauh, Antonia M. Calafat, Allan C. Just, Lori Hoepner, Diurka Diaz, James Quinn, Jennifer Adibi, Frederica P. Perera, Pam Factor-Litvak
Maternal Prenatal Urinary Phthalate Metabolite Concentrations and Child Mental, Psychomotor and Behavioral Development at Age Three Years
Environ Health Perspect. 2011.  doi:10.1289/ehp.1103705 [Online Ahead of Print]

Saillenfait AM, Gallissot F, Sabaté JP.
Differential developmental toxicities of di-n-hexyl phthalate and dicyclohexyl phthalate administered orally to rats.
J Appl Toxicol. 2009 Aug;29(6):510-21.

Grande SW, Andrade AJ, Talsness CE, Grote K, Chahoud I.
A dose-response study following in utero and lactational exposure to di(2-ethylhexyl)phthalate: effects on female rat reproductive development.
Toxicol Sci. 2006 May;91(1):247-54. Epub 2006 Feb 13.

Barbara Kolarika, Carl-Gustaf Bornehaga, Kiril Naydenove, et al
The concentrations of phthalates in settled dust in Bulgarian homes in relation to building characteristic and cleaning habits in the family
Atmospheric Environment. 42(37); Dec 2008: 8553-8559

Lyche JL, Gutleb AC, Bergman A, Eriksen GS, Murk AJ, Ropstad E, Saunders M, Skaare JU.
Reproductive and developmental toxicity of phthalates.
J Toxicol Environ Health B Crit Rev. 2009 Apr;12(4):225-49.

Deblonde T, Cossu-Leguille C, Hartemann P.
Emerging pollutants in wastewater: A review of the literature.
Int J Hyg Environ Health. 2011 Aug 30. [Epub ahead of print]

Yolton K, Xu Y, Strauss D, Altaye M, Calafat AM, Khoury J.
Prenatal exposure to bisphenol A and phthalates and infant neurobehavior.
Neurotoxicol Teratol. 2011 Aug 10. [Epub ahead of print]

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Brain Fog

red-bow-on-fingerThere is a relationship between central nervous system missteps and markers of inflammation. Age doesn’t matter; it happens across the board. If the occasional bout of forgetfulness strikes you, you might recoil in fear of early-onset dementia, especially if the “occasions” are too close together. Is there anything you can do about this? Could it be something you ate? Maybe it’s something you didn’t eat.

Inflammation is a protective response to injury or destruction of tissue that tries to rid the body of the detrimental agent. The process elevates blood markers that are useful in predicting the onset of chronic conditions, such as diabetes or cardiovascular disease. One of these markers is called homocysteine, an amino acid made from methionine that degrades arterial architecture.  But what of mental lapses?  “Epidemiological studies show a positive, dose-dependent relationship between mild-to-moderate increases in plasma total homocysteine concentrations (Hcy) and the risk of neurodegenerative diseases, such as…cognitive impairment…”  (Herrmann.  2011)  Cognitive impairment is not necessarily a sign of impending dementia or Alzheimer’s disease, but elevated homocysteine is “…a surrogate marker for B vitamin deficiency (folate, B12, B6) and a neurotoxic agent.”  (Ibid.)

If you can provide details about your forgetfulness, you don’t have dementia. If you can recall what you read yesterday about the local political scene, you don’t have dementia. If you forgot where you put the car keys, join the crowd.  Nonetheless, you could have homocysteine levels that are too high for your own good.  It’s recognized that taking classes, doing word puzzles, playing chess, and generally challenging the mind can preserve memory.  But these activities won’t necessarily influence renegade body chemistry. Though conjectural, it has been suggested that inflammation disrupts the integrity of the blood-brain barrier, the highly selective membrane that protects the brain from pathogens in the blood, as well as regulates which molecules can pass between the blood and the cerebral spinal fluid. Inflammation compromises the function of the membrane, allowing large molecules access to the brain, resulting in neuronal damage.  (Stolp. 2009).

Herrmann and Obeid (2011) admit that the prospect of improving any degree of neurological distortion caused by homocysteine can be realized with B vitamins. Parallel independent investigation revealed that women with cognitive abasement had higher Hcy values than women without such a burden, and that the folate (a B vitamin also called B9) levels of the affected cohort were measurably lower.  (Faux. 2011)

Homocysteine can be changed back to methionine under the right conditions, namely in the presence of a methylation molecule, such as folic acid (called folate in food). Folate insufficiency, or outright inadequacy, can initiate mental lapses that could balloon into more serious conditions if deficit is prolonged. Therapeutically, folic acid is able to reduce Hcy and the occurrence of neural tube defects in neonates. A side benefit was observed to be the prevention of cervical dysplasia and protection against neoplasm formation in ulcerative colitis.  (Kelly.  1998) Geriatric scientists had indicted homocysteine as causative of neurobehavioral anomalies across a wide range of cognitive domains (Jyme. 2005), and later identified vitamin B12, vitamin B6, and folate (or folic acid) as ameliorative agents.  (Selhub. 2010)

Homocysteine levels do not always increase because of something we did or ate, but because of something we didn’t eat. That would be the foods providing ample supplies of B12, B6, and folic acid.  Certain chronic and contagious diseases that evoke an inflammatory response, even the flu or seasonal allergies, can bring on a foggy mind. Relieving the cause should bring physical relief, and changing the body chemistry should eliminate the fog. All you need is a cue to help you remember that your sunglasses are sitting above your eyebrows.

References

Herrmann W, Obeid R.
Homocysteine: a biomarker in neurodegenerative diseases.
Clin Chem Lab Med. 2011 Mar;49(3):435-41.

Stolp HB, Dziegielewska KM.
Review: Role of developmental inflammation and blood-brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases.
Neuropathol Appl Neurobiol. 2009 Apr;35(2):132-46.

Faux NG, Ellis KA, Porter L, Fowler CJ, Laws SM, Martins RN, Pertile KK, Rembach A, et al
Homocysteine, Vitamin B12, and Folic Acid Levels in Alzheimer’s Disease, Mild Cognitive Impairment, and Healthy Elderly: Baseline Characteristics in Subjects of the Australian Imaging Biomarker Lifestyle Study.
J Alzheimers Dis. 2011 Sep 2.

Kelly GS
Folates: supplemental forms and therapeutic applications.
Altern Med Rev. 1998 Jun;3(3):208-20.

Jyme H. Schafer, MD, MPH; Thomas A. Glass, PhD; Karen I. Bolla, PhD; Margaret Mintz, MS; Anne E. Jedlicka, MS; Brian S. Schwartz, MD, MS
Homocysteine and Cognitive Function in a Population-based Study of Older Adults
J Am Geriatr Soc. 2005;53(3):381-388

Selhub J, Troen A, Rosenberg IH.
B vitamins and the aging brain.
Nutr Rev. 2010 Dec;68 Suppl 2:S112-8.

Schulz RJ.
Homocysteine as a biomarker for cognitive dysfunction in the elderly
Curr Opin Clin Nutr Metab Care. 2007 Nov;10(6):718-23.

Aron M. Troen, Melissa Shea-Budgell, Barbara Shukitt-Hale, Donald E. Smith, Jacob Selhub, and Irwin H. Rosenberg
B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice
PNAS August 26, 2008 vol. 105 no. 34 12474-12479

Roberts RO, Geda YE, Knopman DS, Boeve BF, Christianson TJ, Pankratz VS, Kullo IJ, Tangalos EG, Ivnik RJ, Petersen RC.
Association of C-reactive protein with mild cognitive impairment.
Alzheimers Dement. 2009 Sep;5(5):398-405.

Mancinella A, Mancinella M, Carpinteri G, Bellomo A, Fossati C, Gianturco V, Iori A, Ettorre E, Troisi G, Marigliano V.
Is there a relationship between high C-reactive protein (CRP) levels and dementia?
Arch Gerontol Geriatr. 2009;49 Suppl 1:185-94.

Herrmann W
Significance of hyperhomocysteinemia.
Clin Lab. 2006;52(7-8):367-74.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

B-Vitamins And Memory

confused-young-womanFrancis Bacon, who was a philosopher in the 16th century, said that, “Some books are to be tasted, others swallowed, and some few to be chewed and digested.” The same principle can apply to the written word of the present. If we took everything we read in magazines or over the internet as gospel, conflicting words and ideas would create such confusion that the truth would be more elusive than it has been for decades. While we are able to identify and to reject half-truths in the spoken word, we tend to give them credence if they appear in print. Such is the case with news and reports about the human body and its health and maintenance, and the things we can do and take to guarantee them.

Reports from Fox, Reuters and Medline, among other news services, have said that
B-vitamins can boost memory. Seeing that headline is all some folks need to draw a hasty conclusion, hoping that their loved ones with Alzheimer’s or some other neurological irregularity will be cured. At best, such a conclusion might be drawn following a syllogistic approach, a form of reasoning that relies on major and minor premises:  if this causes this, and if that causes that, then this causes that. Whether or not this is true depends on acceptance of the phrases, “some of the time” and “all of the time.”  Let’s see if we can make sense of the original proposition, that B-vitamins can boost memory.

The study cited by the news services was conducted by Dr. Janine Walker, a mental health researcher from the Australian National University, who reported in the American Journal of Clinical Nutrition that long-term supplementation with folic acid and vitamin B12 promotes improvement in cognitive functioning. (Walker, 2012)  What the headline doesn’t tell us is that the study lasted two years, and that physical exercise was part of the protocol. You have to read the small print, which means the details of the study need to be chewed and digested. The confounding factors and specific provisions must be considered.

Homocysteine (Hcy) is such a factor–and a provision if it’s measureable. Homocysteine is a homologue of the amino acid, cysteine, differing by an additional methylene group (CH2). It’s best known as a marker for inflammation associated with increased risk of cardiovascular disease. Whether or not lowering homocysteine will also lower CVD risk is still under examination, but it has been accepted that raised Hcy is associated with poor cognitive performance in the general population, not only in the elderly. Increases in serum folic acid levels are accompanied by decreases in Hcy levels. (Durga, 2007)  But this doesn’t mean that cognitive function will automatically improve. It takes time, another factor to be weighed. After three years of folic acid supplementation, Durga and his Dutch colleagues learned that the molecule, did, in fact, improve specific domains of cognitive function, particularly those that decline with age. What we are not told is that folic acid (vitamin B9) works best in the company of vitamins B12 and B6, where its role as a promoter of brain function can be fully realized.

If there is a pin to be put into this balloon, it comes courtesy of the Cochrane Database and its systematic reviews of primary research in health care and health policy. One of its 2008 reviews examined the effects of folic acid on demented people and their cognitive shortcomings, only to announce that no consistent evidence supports the use of folic acid—with or without vitamin B12—to effect improvement. They are carefully deliberate to add, however, that long-term use of folic acid (also known as folate in foods) does appear to improve the cognitive function of those individuals with elevated homocysteine levels. (Malouf, 2008)  Do you see the factor?  Long-term use.

Many elderly present with movement disorders to some degree. Swedish investigators looked at a population of community-dwelling septuagenarians who suffered both movement and cognitive disadvantages, treating them with vitamins B9, B6, and B12. More than 60% of the men and almost 50% of the women had high Hcy levels and high methylmalonic acid (MMA) concentrations, the latter indicating B12 deficiency. Vitamin therapy lowered both markers, but failed to mitigate both the movement and cognitive deficits. This does not mean the therapy is useless, though. The report allows that dosage could have been too low to prove effective, or that the physical and mental declines could have become irreversible. (Lewerin, 2005)  If such decline is recognized at all, could it / should it have been identified years—or even decades—sooner?   With all illness and debility, isn’t that ounce of prevention worth lots more than the pounds of cure?   To be considered also is that stores of nutrients decline sharply with age. For how long were they deficient?  How about the form of the nutrient?  Methylcobalamin is the much preferred form of vitamin B12, but the Swedish study used cyanocobalamin, a form that is unnatural to plants and animals. And, it contains an “insignificant” amount of cyanide that still must be eliminated from the body. Isn’t the mere four months duration of this study too little time to come to a righteous conclusion?  The factor?  Time.

“Over the short or medium term,” announces a Glasgow paper, cognitions did not improve with the vitamin cocktail. This study population, older than sixty-five and comparatively small at 185 participants, suffered ischemic vascular disease, that which decreases blood supply to an organ by constricting a blood vessel. Since all ischemia is not the same for all people, that condition might just confound the matter. This study lasted three months to one year. Here is a senior population with constrictive vascular disease, probably taking one or more medications, whose compliance is not monitored, with unknown dietary habits and unmentioned polypharmacy, and possibly experiencing other health issues. (MacDonald, 2005). Are we expected to accept the conclusion without question?

In ameliorative protocols where the patient is ambulatory, exercise is warranted, either as an isolated or as a supportive element. (Wen, 2010)  (Harkcom, 1085)  (Kirkcaldy, 1990)  Nonetheless, the administration of selected B-vitamins has an effect on the factors that interfere with brain function and memory, if only because they can mitigate the adverse effects of inflammation. Homocysteine is a documented CVD factor that is related to both vascular dementia and Alzheimer’s disease. (Stabler, 2003)  It appears that the attenuation of Hcy with folic acid, vitamin B6 and vitamin B12, accompanied by a modicum of exercise, and conducted over a reasonable period of time, can yield the desired result in cognitive change. IF homocysteine is related to cognitive decline, and IF a B-vitamin cocktail reduces homocysteine, THEN the cocktail may be able to reverse faulty cognition (in certain circumstances). Because these supplements are water-soluble, toxicity is of little concern regardless of the elevated dosage required.

References

Durga J, van Boxtel MP, Schouten EG, Kok FJ, Jolles J, Katan MB, Verhoef P.
Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial.
Lancet. 2007 Jan 20;369(9557):208-16.

Feng L, Ng TP, Chuah L, Niti M, Kua EH.
Homocysteine, folate, and vitamin B-12 and cognitive performance in older Chinese adults: findings from the Singapore Longitudinal Ageing Study.
Am J Clin Nutr. 2006 Dec;84(6):1506-12.

Ford AH, Flicker L, Alfonso H, Thomas J, Clarnette R, Martins R, Almeida OP.
Vitamins B(12), B(6), and folic acid for cognition in older men.
Neurology. 2010 Oct 26;75(17):1540-7.

Garcia A, Zanibbi K.
Homocysteine and cognitive function in elderly people.
CMAJ. 2004 Oct 12;171(8):897-904.

Thomas M. Harkcom MD, Richard M. Lampman PhD, Barbara Figley Banwell PT, C. William Castor MD
Therapeutic value of graded aerobic exercise training in rheumatoid arthritis
Arthritis & Rheumatism. Volume 28, Issue 1, pages 32–39, January 1985

Kirkcaldy, Bruce D.;Shephard, Roy J.
Therapeutic implications of exercise.
International Journal of Sport Psychology, Vol 21(3), Jul-Sep 1990, 165-184.

Lewerin C, Matousek M, Steen G, Johansson B, Steen B, Nilsson-Ehle H.
Significant correlations of plasma homocysteine and serum methylmalonic acid with movement and cognitive performance in elderly subjects but no improvement from short-term vitamin therapy: a placebo-controlled randomized study.
Am J Clin Nutr. 2005 May;81(5):1155-62.

Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr; Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators.
Homocysteine lowering with folic acid and B vitamins in vascular disease.
N Engl J Med. 2006 Apr 13;354(15):1567-77.

Malouf R, Grimley Evans J.
Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people.
Cochrane Database Syst Rev. 2008 Oct 8;(4):CD004514.

McCaddon A, Hudson P, Davies G, Hughes A, Williams JH, Wilkinson C
Homocysteine and cognitive decline in healthy elderly.
Dement Geriatr Cogn Disord. 2001 Sep-Oct;12(5):309-13.

McCaddon, Andrew
Homocysteine and cognitive impairment; a case series in a General Practice setting
Nutrition Journal. 15 February 2006, 5:6

Oulhaj A, Refsum H, Beaumont H, Williams J, King E, Jacoby R, Smith AD.
Homocysteine as a predictor of cognitive decline in Alzheimer’s disease.
Int J Geriatr Psychiatry. 2010 Jan;25(1):82-90.

Sally P Stabler
Vitamins, homocysteine, and cognition
American Journal of Clinical Nutrition, Vol. 78, No. 3, 359-360, September 2003

A. David Smith, Stephen M. Smith, Celeste A. de Jager, Philippa Whitbread, Carole Johnston, Grzegorz Agacinski, Abderrahim Oulhaj, Kevin M. Bradley, Robin Jacoby, Helga Refsum
Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial
PLoS ONE. September 8, 2010; 5(9): e12244.

Stott DJ, MacIntosh G, Lowe GD, Rumley A, McMahon AD, Langhorne P, Tait RC, O’Reilly DS, Spilg EG, MacDonald JB, MacFarlane PW, Westendorp RG.
Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease.
Am J Clin Nutr. 2005 Dec;82(6):1320-6.

van Uffelen JG, Chin A Paw MJ, Hopman-Rock M, van Mechelen W.
The effect of walking and vitamin B supplementation on quality of life in community-dwelling adults with mild cognitive impairment: a randomized, controlled trial.
Qual Life Res. 2007 Sep;16(7):1137-46.

van Uffelen JG, Chinapaw MJ, van Mechelen W, Hopman-Rock M.
Walking or vitamin B for cognition in older adults with mild cognitive impairment? A randomised controlled trial.
Br J Sports Med. 2008 May;42(5):344-51.

Walker JG, Batterham PJ, Mackinnon AJ, Jorm AF, Hickie I, Fenech M, Kljakovic M, Crisp D, Christensen H.
Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms–the Beyond Ageing Project: a randomized controlled trial.
Am J Clin Nutr. 2012 Jan;95(1):194-203.

Wen D, Xu J, Xie X, Zhang J, Zhong Y, Sun Y, Duan Y.
Effect of physical exercise on the efficacy of mitoxantrone-loaded nanoparticles in treating early breast cancer.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2010 Feb;27(1):109-12.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Menopause and Memory

Coping with the menopauseFor eras women’s physical and mental suffering has been trivialized when it is associated with the condition of menopause.  But the reality of hot flashes, fatigue, sleep disturbance, moodiness, and discomfiting cerebral performance during menopause is virtually tangible.   Various traditional and alternative therapies are used to address these symptoms, from hormone replacement therapy at the allopathic end to black cohosh and essential fatty acids at the complementary end. The brain fog, on the other hand, has been viewed with less fervor until recently.

The Department of Neurology at the University of Rochester, In New York, reported that the memory problems described by women as menopause approaches are real (Weber, Mapstone, et al, 2012). Of course, this is nothing new to the millions of women who have had periods of forgetfulness or fogginess in their 40s and 50s.  Their experiences have been validated by a rigorous battery of cognitive tests administered by researchers at Rochester and the U. of Illinois at Chicago.  The goal of the study was to find a relationship between subjective reports of memory complaints and objective tests of cognitive function, described as the intellectual process by which a person perceives and comprehends ideas.   Included here are all aspects of thought, reason, and recollection.   Antipodal is the brain misstep that affects all ages and is characterized by confusion, decreased clarity of thought, and forgetfulness.  In some folks this can lead to minor depression on the one hand and delinquency on the other.  For as often as this happens to women all over the globe, it still is barely seen as a “real” condition.

The subjects who participated in the study completed a comprehensive neuropsychological battery of tests that measured attention, working memory, verbal memory and fluency, visual-spatial skills, and fine motor dexterity.  Self-report inventories of perceived memory symptoms were included.  The findings indicated a link between the subjective memory faults and actual memory deficits in some, but not all, realms.  Working memory and complex attention tasks were most affected.  Working memory is the ability to hold information in the mind long enough to perform a complex task regardless of interfering processes and distractions.  If this operation is hindered, the person is frustrated.  If this recurs, the presentation of depressive symptoms should not be a complete surprise.  The physical changes of menopause are identifiable, but the mental changes are not to be identified with the mental aberrations of dementia.  Menopausal women can rate their own memory skills; demented ones cannot.

Brain fog can be triggered by physical, psychological, biochemical and even spiritual factors.  Some of these are adrenal exhaustion, food and chemical reactions, stress, and nutritional deficiencies.  There are, however, age-related cognitive changes that, though of non-dementia origin, can interfere with a person’s daily functioning, which makes this a relevant clinical issue.  Overcoming this situation may be as simple as getting enough sleep, exercising, or eating the right foods.  Meditation and prayer have been used as first-line treatment in some venues.  While the complex relationship of mood, memory and hormones is not identical in every case, it is inferred that the amount of attention paid to a novel situation or perception influences the persistence of memory (Weber & Mapstone, 2009).  Overall, if a woman says she experiences disconcerting bouts of forgetfulness, she deserves confirmation that these cognitive signs are part of the array of menopause symptoms (Schaafsma, 2010).

There are factors in the aging process that interact with menopause itself, among them  homocysteine values, hypercholesterolemia, metabolic syndrome or type 2 diabetes, hypertension, and depression.   If drugs are used to address any of these concerns, and if a drug has anticholinergic properties, there likely will be cognitive impairment to some degree.  This compounds the matter, and may lead to improper diagnoses and unneeded treatment for a condition that does not really exist.  This class of drugs—the anticholinergics—is used to treat gastric disturbances, urinary problems, respiratory matters, and insomnia, among others disorders that may display themselves as menopause signs in the first place.

The use of hormones to improve mental function in menopause has been hit and miss.  Observational studies say one thing, while randomized clinical trials report something else.   In a Wake Forest University study it was concluded that using estrogen with progestin to mediate global cognitive function in women over age 65 was less effective than the placebo.  In fact, it increased cognitive decline (Rapp, 2003).  While no clinically relevant adverse effects were reported, the trial was stopped because of “certain increased health risks for women” (Ibid.).  Hedging its bets, another study, following a similar protocol, found a negative effect on verbal memory, but a “trend to” a positive impact on figural memory, with other domains unaffected by the combination of estrogen and progestin (Resnick, 2006).  For those who put all their eggs into one basket—the basket of allopathic medicine and Big Pharma—this is an eye-opener.

Walking down the primrose path, we stumble upon complementary medicine or functional medicine or integrative medicine, all of which are supported by evidence-based science, none of which is a sham.  Because it can’t be a money-maker for mega-corporations, since natural substances cannot be patented, complementary medicine raises a jaundiced eye.  And because your physician has little time to examine the research for himself, being directed by the verbal testimonies of the pharmaceutical representative, he knows little or nothing about the efficacy of alternative modalities.

It’s uncertain whether money, time, compassion, or philosophy drives the Euro-Asian medical community to study alternatives to allopathic treatment more earnestly than happens in the States.  Studies on ginkgo biloba that were performed in the last century in the UK have determined that this extract has profound impact on working memory and psychomotor performance at doses of 120 mg a day, with those between ages 50-59 reaping the most benefit (Rigney, 1999).  An earlier study, employing 600 mg of ginkgo extract, found significant improvement in memory one hour after administration (Subhan, 1984).  If there is concern that these studies are too old to carry any weight, work done in this century agrees (Scholey, 2002) (Kennedy, 2000) In order to “kick it up a notch,” scholars of neuroscience and cognition, also in the UK, decided to combine ginkgo with Panax ginseng—the adaptogen that purportedly increases the body’s resistance to stress, anxiety and fatigue—and to measure the combined efficacy on cognitive benefit in tests of serial arithmetic tasks with varying cognitive load and in tests of memory quality.  Two studies found this phytopharmaceutical blend to offer substantial cognitive profit (Wesnes, 2000) and (Scholey, 2002)

Why settle for cognitive improvement alone when the whole body can capitalize on a protocol?  Ever hear of phosphatidylcholine?  It’s the number one phospholipid from which you are made.  It’s a component of each of the trillions of cells that make you, you.  You’ve heard the expression, “When Mama’s happy, everybody’s happy?”  When the cells are healthy, everything is healthy.  That’s what phosphatidylcholine (PC) does:  it restores and elevates cellular function and stability.    And it enhances learning and memory, and improves cognitive disorders (Nagata, 2011) (Fioravanti, 2005)  As an unseen but additional benefit, PC is accompanied in its extraction by phosphatidylethanolamine, a phospholipid that helps to manufacture phosphatidylserine, an ingredient known to attenuate many neuronal effects of aging, and to restore normal memory on a variety of tasks (McDaniel, 2003)  It’s possible to lift that fog, after all.

References

Fioravanti M, Yanagi M.
Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly.
Cochrane Database Syst Rev. 2005 Apr 18;(2):CD000269.

Kennedy DO, Scholey AB, Wesnes KA.
The dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers.
Psychopharmacology (Berl). 2000 Sep;151(4):416-23.

McDaniel MA, Maier SF, Einstein GO.
“Brain-specific” nutrients: a memory cure?
Nutrition. 2003 Nov-Dec;19(11-12):957-75.

Nagata T, Yaguchi T, Nishizaki T.
DL- and PO-phosphatidylcholines as a promising learning and memory enhancer.
Lipids Health Dis. 2011 Jan 28;10:25.

Park DC, Smith AD, Lautenschlager G, Earles JL, Frieske D, Zwahr M, Gaines CL.
Mediators of long-term memory performance across the life span.
Psychol Aging. 1996 Dec;11(4):621-37.

Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner RL, Manson JE, Gass ML, Stefanick ML, Lane DS, Hays J, Johnson KC, Coker LH, Dailey M, Bowen D; WHIMS Investigators.
Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial.
JAMA. 2003 May 28;289(20):2663-72.

Resnick SM, Maki PM, Rapp SR, Espeland MA, Brunner R, Coker LH, Granek IA, Hogan P, Ockene JK, Shumaker SA; Women’s Health Initiative Study of Cognitive Aging Investigators.
Effects of combination estrogen plus progestin hormone treatment on cognition and affect.
J Clin Endocrinol Metab. 2006 May;91(5):1802-10. Epub 2006 Mar 7.

Rigney U, Kimber S, Hindmarch I.
The effects of acute doses of standardized Ginkgo biloba extract on memory and psychomotor performance in volunteers.
Phytother Res. 1999 Aug;13(5):408-15.

Schaafsma M, Homewood J, Taylor A.
Subjective cognitive complaints at menopause associated with declines in performance of verbal memory and attentional processes.
Climacteric. 2010 Feb;13(1):84-98.

Scholey AB, Kennedy DO.
Acute, dose-dependent cognitive effects of Ginkgo biloba, Panax ginseng and their combination in healthy young volunteers: differential interactions with cognitive demand.
Hum Psychopharmacol. 2002 Jan;17(1):35-44.

Subhan Z, Hindmarch I.
The psychopharmacological effects of Ginkgo biloba extract in normal healthy volunteers.
Int J Clin Pharmacol Res. 1984;4(2):89-93.

Weber M, Mapstone M.
Memory complaints and memory performance in the menopausal transition.
Menopause. 2009 Jul-Aug;16(4):694-700.

Weber MT, Mapstone M, Staskiewicz J, Maki PM.
Reconciling subjective memory complaints with objective memory performance in the menopausal transition.
Menopause. 2012 Mar 12. [Epub ahead of print]

Wesnes KA, Ward T, McGinty A, Petrini O.
The memory enhancing effects of a Ginkgo biloba/Panax ginseng combination in healthy middle-aged volunteers.
Psychopharmacology (Berl). 2000 Nov;152(4):353-61.

Wilson RS, Beckett LA, Barnes LL, Schneider JA, Bach J, Evans DA, Bennett DA.
Individual differences in rates of change in cognitive abilities of older persons.
Psychol Aging. 2002 Jun;17(2):179-93.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Low Cholesterol And Mental Health

sad-eggsIf mental health is defined as a state of emotional and psychological well-being in which an individual is able to use his or her cognitive and emotional capabilities, function in society, and meet the ordinary demands of everyday life, then we need to take care of the garage in which this vehicle is kept.  Measures of depression and anxiety assess things such as self-disparagement, pessimism, lack of drive, apprehension, inability to relax, and irritability, to name a few.  Interestingly, these evaluations have demonstrated a relationship to low lipid and lipoprotein concentrations.

In work done at the end of the last century, an inverse association between mental challenges and total cholesterol and lipids was found.  That means when one goes up, the other goes down.  Testing young adult females, Duke University Medical Center discovered that women “…with low total cholesterol concentrations (<4.14 mmol/liter) relative to those with moderate to high cholesterol levels, were more likely to have higher scores on the NEO depression subscale…and anxiety subscale…” after adjustments were made for age, body mass index, oral contraceptive use and physical activity.  (Suarez.  1999)

Before we got too involved, it pays to know that 4.14 mmol/liter is equal to a cholesterol level of 160 mg/dL, or just plain 160.  Cholesterol is a steroid substance necessary to human life.  It forms the cell membranes in all organs and tissues of the body, is essential to the production of the hormones we need for growth, development, and reproduction, and it makes the bile acids necessary for absorption of nutrients.  Very little, if any, dietary cholesterol becomes serum cholesterol.

Back in the 1990’s it was noted that cholesterol levels below 160 were tied to excess mortality from all causes, primarily from a variety of cancers, respiratory and digestive diseases, and violent deaths from suicide and trauma.  Reasons behind low cholesterol have been ascribed to genetics, resistance to dietary sources, acute infections, and alcohol use/abuse.  (Meilahn.  1995)  If suicide is tied to depression, then it may be a legitimate effect.  Depression is twice as common among women as men, with about one in four suffering at some point in her lifetime.  The greatest vulnerability appears during the childbearing years, the time when its diagnosis is often overlooked.  The turbulence of hormones flooding a woman’s system at different times and in differing amounts can surely be a potent stressor.

Scientists in Barcelona, Spain, realized the connection of cholesterol to neuropsychiatric disease in a review of related literature that preceded their interest.  They found a link to early death, suicide and aggression, and personality disorders and dementia. (Martinez-Carpio.  2009). It appears that the good intentions of reducing what was thought to be the cause of cardiac mortality opened a different can of worms.  The Japanese explored the intrigue that was sparked when total mortality was not reduced despite reduction of mortality due to coronary heart disease, and found an increase in death rates due to suicide and accidents, many of which were tied to risky behaviors in persons with low cholesterol levels.  (Kunugi.  2001)  Does low cholesterol compromise judgment?  The U. of California conducted trials in the early 90’s to determine the cause behind the rise in suicides in men older than fifty years, and found that depression was three times more prevalent in those whose cholesterol was lower than 160.  Health status, number of chronic diseases, number of medications, and exercise seemed not to have had an adverse effect on depressive signs and symptoms. This led to the suggestion that the intentional lowering of cholesterol be more deliberate.  (Morgan. 1993)

Cedars-Sinai Medical Center, in Los Angeles, reported that serotonin, a neurotransmitter that controls impulsive behaviors, is tied to cholesterol levels at the synapses.  Low membrane cholesterol decreases the number of serotonin receptors, thereby reducing suppression of aggressive and destructive behaviors.  (Engelberg. 1992)  That magic number, 160, once again made headlines in the Netherlands, where epidemiologists discovered a higher prevalence of depression in males whose cholesterol was below that level.  (Steegmans. 2000)  Low cholesterol was cited as causative to rises in criminal violence in Sweden, following the association of reduced cholesterol values to low serotonin activity. (Golomb. 2000)  Reduced levels of total cholesterol, LDL, and HDL resulted in minimized serotonin values in personality disordered cocaine users, as reported by addiction researchers in their journal. (Buydens-Branchey. 2000)  In school-aged children, those with cholesterol values lower than 145 were three times more likely to have been suspended or expelled from school.  This is an absolute consideration, and has nothing to do with socio-economic status or ethnic background, nor with nutrition status or academic achievement.  (Zhang. 2005)

Life is supposed to be a balancing act.  Lots of us overdo something.  The balance between total cholesterol and HDL can allay fears of cardiovascular disease, despite cholesterol in the 200 range.  Cholesterol levels below 170 can make us irritable…and irritating.

References

Suarez EC.
Relations of trait depression and anxiety to low lipid and lipoprotein concentrations in healthy young adult women.
Psychosom Med. 1999 May-Jun;61(3):273-9.

Elaine N. Meilahn, MD
Low Serum Cholesterol  Hazardous to Health?
Circulation. 1995;92:2365-2366

Martínez-Carpio PA, Barba J, Bedoya-Del Campillo A.
[Relation between cholesterol levels and neuropsychiatric disorders].  [Article in Spanish]
Rev Neurol. 2009 Mar 1-15;48(5):261-4.

Kunugi H.
[Low serum cholesterol and suicidal behavior].  [Article in Japanese]
Nihon Rinsho. 2001 Aug;59(8):1599-604.

Morgan RE, Palinkas LA, Barrett-Connor EL, Wingard DL.
Plasma cholesterol and depressive symptoms in older men.
Lancet. 1993 Jan 9;341(8837):75-9.

Engelberg H.
Low serum cholesterol and suicide.
Lancet. 1992 Mar 21;339(8795):727-9.

Paul H. A. Steegmans, MD, Arno W. Hoes, MD, PhD, Annette A. A. Bak, MD, PhD, Emiel van der Does, MD, PhD and Diederick E. Grobbee, MD, PhD
Higher Prevalence of Depressive Symptoms in Middle-Aged Men With Low Serum Cholesterol Levels
Psychosomatic Medicine 62:205-211 (2000)

Beatrice A Golomb, Håkan Stattin, Sarnoff Mednick
Low cholesterol and violent crime
Journal of Psychiatric Research. Volume 34, Issue 4 , Pages 301-309, July 2000

Laure Buydens-Branchey, Marc Branchey, Jeffrey Hudson, Paul Fergeson
Low HDL cholesterol, aggression and altered central serotonergic activity
Psychiatry Research. Volume 93, Issue 2 , Pages 93-102, 6 March 2000

Zhang J, Muldoon MF, McKeown RE, Cuffe SP
Association of serum cholesterol and history of school suspension among school-age children and adolescents in the United States.
Am J Epidemiol 2005; 161:691-9.

Scanlon SM, Williams DC, Schloss P.
Membrane cholesterol modulates serotonin transporter activity
Biochemistry. 2001 Sep 4;40(35):10507-13.

Laure Buydens-Branchey,a Marc Branchey,a and Joseph R. Hibbelnb
ASSOCIATIONS BETWEEN INCREASES IN PLASMA N-3 POLYUNSATURATED FATTY ACIDS FOLLOWING SUPPLEMENTATION AND DECREASES IN ANGER AND ANXIETY IN SUBSTANCE ABUSERS
Prog Neuropsychopharmacol Biol Psychiatry. 2008 February 15; 32(2): 568–575.

BRIAN HALLAHAN, MRCPsych and MALCOLM R. GARLAND, MRCPsych
Essential fatty acids and mental health
The British Journal of Psychiatry (2005) 186: 275-277

Hillbrand M, Waite BM, Miller DS, Spitz RT, Lingswiler VM
Serum cholesterol concentrations and mood states in violent psychiatric patients: an experience sampling study.
J Behav Med 2000; 23:519-29.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Alzheimer’s Disease And Visual Clutter

senior-coupleSuppose you were at a football game where the home team spectators were wearing red hats, but your sister was wearing a yellow one because nobody told her that today was red hat day. Could you pick her out of the crowd? Kind of easy, right? Now, suppose one of her friends gave your sister the extra red hat she carried in her tote bag.  Finding her in the crowd would be more of a challenge, eh? What is it that causes the confusion? Is it the hat or that your sister tends to look like everyone else? How sorry do you feel for the guy who comes to work wearing one maroon and one brown sock because he is retinal rod-deficient and has a hard time distinguishing shades (despite that he has another pair just like this one)? Under some circumstances, recognition can be a challenge, particularly when crowding of images occurs, as in both the stadium and the sock drawer. Such is the trial of the Alzheimer’s or the mildly demented patient, only it happens more often.

Those with Alzheimer’s disease may be unable to recognize once-familiar faces and objects because of infirm perceptions or the incapacity to recall from memory. The face is important to social interaction. Its perceptions are complexed by the myriad facial expressions and shapes that need to be analyzed and interpreted. Additionally, context affects recognition. Although you’ve seen a colleague in the office day after day for years, you may suddenly forget his name when seeing him, after your or his retirement, in a venue that is unfamiliar to both of you, such as a shopping mall in a distant city.  Face perception involves more than one area of the brain, with some areas being more important than others. One of these is called the medial temporal lobe, a kind of garage that houses the memory “toolbox,” most notably the hippocampus, the part that is critical to memory formation. In here sits the perihinal cortex, which receives data from the sense organs. It favors visual perception and memory while the rest of the hippocampus processes spatial and temporal relationships (Murray, 2007) (Buckley, 2005).

Damage to, or interference with, the perihinal cortex or its immediate surroundings can hamper the availability of semantic (long-term factual) memory and the formation of new memories from recent perceptions. The capacity to attach meaning to new percepts is compromised, and memories are not completely formed. Because faces share common features, ambiguity of interpretation can occur and recognition becomes an uncertain proposition. Recognition of faces may also be tied to events. Reliving the past, using episodic memory, may be able to jar recall, but not always and not always with the same reliability. Impairment of episodic memory is the hallmark of Alzheimer’s disease, but in some circles is viewed more as the inability to encode and store information than an inability to retrieve it (Traykov, 2007).

Because perception and memory are linked, it is possible that one affects the other.  Your mentally challenged aunt may fail to recognize you not only because she forgot who you are, but also because she can’t clearly perceive the distinct combination of facial features that make you, you. But this is more apt to happen in a crowd of other, competing, faces than if you walk into her room by yourself. It’s been determined that minimizing the degree of perceptual interference can improve facial/object perception by eliminating features that are visually similar. Low interference conditions, where perceptually dissimilar objects occupy proximal space, present less visual clutter, often resulting in improved cognitive performance (Newsome, 2012). The less feature ambiguity, the more meaningful the perceptual representation (Barense, 2010). This means that a person with a square facial feature would be more easily recognizable than if he had a rounded feature, like everybody else. Thus, if the whole family comes to visit your demented aunt, it can be supposed that entering the room one at a time, allowing her to react and to respond to one face at a time, may be more positive an encounter  that entering en masse. Object or facial recognition in clutter may also depend on whether or not the original perception occurred in visual clutter, which purportedly has an effect on later discrimination. Meeting a person for the first time while in a large group, compared to meeting him in a twosome or threesome, will have an effect on the recognition of that person at a later time, whether alone or not. Unless special attention is paid to new perceptions, memory lapses should not be a surprise.  Visual clutter demands competitive selection, and reducing clutter could help not only the cognitively impaired with everyday tasks, but also the inattentive, distracted or disinterested people around us.

Everyone sometimes has trouble recognizing faces, and it’s even more common for people to forget names. There is a name for face “blindness.” It’s prosopagnosia. One of the complaints of sufferers is that they can’t follow the plot of a TV serial because they don’t recognize the characters they saw on the previous show. Most cases involve brain damage, including that from trauma, stroke or the degeneration of AD. In these instances, face recognition was normal at one time. Of course, this can cause serious social problems, but it is downright frightening when people cannot recognize themselves in a mirror.

References

Barense MD, Rogers TT, Bussey TJ, Saksida LM, Graham KS.
Influence of conceptual knowledge on visual object discrimination: insights from semantic dementia and MTL amnesia.
Cereb Cortex. 2010 Nov;20(11):2568-82.

Barense MD, Ngo JK, Hung LH, Peterson MA.
Interactions of memory and perception in amnesia: the figure-ground perspective.
Cereb Cortex. 2012 Nov;22(11):2680-91.

Buckley MJ.
The role of the perirhinal cortex and hippocampus in learning, memory, and perception.
Q J Exp Psychol B. 2005 Jul-Oct;58(3-4):246-68.

Duarte LR, Syssau A, Jiménez M, Launay M, Terrier P.
Deficit of access or storage: semantic memory processing in Alzheimer disease.
Can J Aging. 2007 Fall;26(3):227-39.

Jay Hegdé, Serena K. Thompson, Mark Brady and Daniel Kersten
Object recognition in clutter: cortical responses depend on the type of learning
Front. Hum. Neurosci. 6:170. Publ online: 19 June 2012.

Laisney M, Giffard B, Eustache F.
Semantic memory in Alzheimer’s disease: contributions of semantic priming.
Psychol Neuropsychiatr Vieil. 2004 Jun;2(2):107-15.

McCarley, Jason S.; Yamani, Yusuke; Kramer, Arthur F.; Mounts, Jeffrey R. W.
Age, clutter, and competitive selection.
Psychology and Aging, Vol 27(3), Sep 2012, 616-626.

Murray EA, Bussey TJ, Saksida LM.
Visual perception and memory: a new view of medial temporal lobe function in primates and rodents.
Annu Rev Neurosci. 2007;30:99-122.

Elisabeth A. Murray, Steven P. Wise
Why is there a special issue on perirhinal cortex in a journal called hippocampus? The perirhinal cortex in historical perspective
Hippocampus–Special Issue: Perirhinal Cortex: At the Crossroads of Memory and Perception
Volume 22, Issue 10, pages 1941–1951, October 2012

Rachel N. Newsome, Audrey Duarte, Morgan D. Barense
Reducing perceptual interference improves visual discrimination in mild cognitive impairment: Implications for a model of perirhinal cortex function
Hippocampus–Special Issue: Perirhinal Cortex: At the Crossroads of Memory and Perception
Volume 22, Issue 10, pages 1990–1999, October 2012

Traykov L, Rigaud AS, Cesaro P, Boller F.
Neuropsychological impairment in the early Alzheimer’s disease.
Encephale. 2007 May-Jun;33(3 Pt 1):310-6.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Is Your Hippocampus On A Hippo Campus?

strong-brainWell, if you have half a mind, you have a whole hippocampus. It’s the part of the brain in charge of long-term memory (Where are the car keys?) and spatial relations (Will this car fit into that parking space?). It’s shaped like a horseshoe and straddles both of the brain’s hemispheres.  It works like a book’s index, where it consolidates new memories and helps to retrieve them later on. It’s the search engine of the brain. Depending on the perceived importance of a task or episode, learning and remembering may require only a single exposure, after which the memory trace either disappears or consolidates into the long-term cache.

Neuroscientists use rats and mice in their investigations. This is an intriguing proposition to non-scientists, who are not aware that all mammalian hippocampi tend to work the same way. The anatomy, physiology and genetics of mice and rats are strikingly similar to humans’, where 95% of their genome is shared. Rats are the subjects of study because they mature quickly and have brains large enough to make observations easy. About the only part of the brain that separates us from rats is the prefrontal cortex with its higher-level thought processes, such as setting goals, reminiscing, and inhibiting irrelevant functions.

To exemplify the parallels, scientists exposed rats to environments that were enriched, standard or impoverished. Later, their brains were examined, finding that the structures of the enriched had more and longer dendrites, which afford more opportunity for learning and memory. Post-mortem brain tissue of college-educated humans was compared with that of lesser-educated humans, also finding more and longer dendrites, leading to the conclusion that brain changes—multiplying connections—occur in response to a complex environment (Jacobs, 1993) (Diamond, 1972, 2001).

Diets high in saturated fats and refined sugars may cause changes in the brain that fuel the overconsumption of foods that make people gain weight. Such cerebral alterations happen in spite of the mental stimulation that encourages positive brain development.  In this vicious cycle lies a possible explanation why obesity is so hard to overcome—the brain says to keep eating while blocking thoughts of self-control. Lab rats offered unlimited access to a high-energy diet (high-fat/high-calorie) fared much worse in memory tests than their cohorts fed the opposite, indicating to researchers a change in functionality of the hippocampus (Davidson, 2012). In effect, they “forgot” to stop eating. It appears that saturated fats and refined sugars interfere with messages that tell you when to rein it in. Diet-induced obesity has such deleterious effects on the hypothalamus that more time becomes necessary to learn new tasks and more errors occur along the way (Valladolid-Acebes, 2011).

Excess energy intake, especially if combined with a sedentary lifestyle, is associated with a number of conditions that include cardiovascular disease, insulin resistance/diabetes, and some cancers. But this elevated risk of cognitive decline in later life is something that can be contained with conscious effort. Public health messages have decried the scourge of obesity for a time, but have never made known its association with mental dilapidation (Sabia, 2009). For those memories maintained by the hippocampus, the edge goes to people of normal weight (Nilsson, 2009).

Neural plasticity refers to the change in structure, function and organization of neurons in response to new learning experiences, where nerve connection are added based on outside stimuli, as mentioned earlier. Some researchers have reported sex differences in response to high-fat and high-sucrose diet, where females are less vulnerable to its impact (Hwang, 2010). This relative immunity from cognitive compromise does little for connubial bliss.  We need to note, though, that some types of learning and memory may be affected by diet more than others. For example, memory retention but not acquisition may suffer. We also know that sugar intake has an effect on triglycerides, the reduction of which could reduce cognitive impairment while improving cardiac health. That may be worth a look.

There is considerable data from animal studies and somewhat more limited data from human studies to support the premise that excess energy intake drives cognitive dysfunction and disrupts neural plasticity. Because of individual differences—genetics, exercise, lifestyle—it’s not likely that science can make recommendations about the ideal energy intake, although an upper limit of 2200 calories for men and 2000 calories for women has been proposed. Meanwhile, exercise is recognized as a major factor in mediating the adverse effect of sloppy diet on cognitive wherewithal (van Praag, 2009), followed by increase in social interaction or engaging in challenging activities such as some hobbies afford (Bennett, 2006). So, now when you watch what you eat, watch what you eat. Eating to live is not the same as living to eat.

References

Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C, Dartigues JF, Alpérovitch A.
Dietary patterns and risk of dementia: the Three-City cohort study.
Neurology. 2007 Nov 13;69(20):1921-30.

Bennett DA, Schneider JA, Tang Y, Arnold SE, Wilson RS.
The effect of social networks on the relation between Alzheimer’s disease pathology and level of cognitive function in old people: a longitudinal cohort study.
Lancet Neurol. 2006 May;5(5):406-12.

Terry L. Davidson, Andrew Monnot, Adelai U. Neal, Ashley A. Martin, J. Josiah Horton,
Wei Zheng
The effects of a high-energy diet on hippocampal-dependent discrimination performance and blood–brain barrier integrity differ for diet-induced obese and diet-resistant rats
Physiology & Behavior. Volume 107, Issue 1, 20 August 2012, Pages 26–33

DeKosky ST, Abrahamson EE, Ciallella JR, Paljug WR, Wisniewski SR, Clark RS, Ikonomovic MD.
Association of increased cortical soluble abeta42 levels with diffuse plaques after severe brain injury in humans.
Arch Neurol. 2007 Apr;64(4):541-4.

Marian C. Diamond, Mark R. Rosenzweig, Edward L. Bennett, Bernice Lindner, Lennis Lyon
Effects of environmental enrichment and impoverishment on rat cerebral cortex
Journal of Neurobiology.  Volume 3, Issue 1, pages 47–64, 1972

Diamond MC.
Response of the brain to enrichment.
An Acad Bras Cienc. 2001 Jun;73(2):211-20.

Carol E. Greenwood, Gordon Winocur†
Learning and memory impairment in rats fed a high saturated fatdiet
Behavioral and Neural Biology. Volume 53, Issue 1, January 1990, Pages 74–87

Hendrickx H, McEwen BS, Ouderaa F.
Metabolism, mood and cognition in aging: the importance of lifestyle and dietary intervention.
Neurobiol Aging. 2005 Dec;26 Suppl 1:1-5. Epub 2005 Nov 14.

Hwang LL, Wang CH, Li TL, Chang SD, Lin LC, Chen CP, Chen CT, Liang KC, Ho IK, Yang WS, Chiou LC.
Sex differences in high-fat diet-induced obesity, metabolic alterations and learning, and synaptic plasticity deficits in mice.
Obesity (Silver Spring). 2010 Mar;18(3):463-9. Epub 2009 Sep 3.

Jacobs B, Schall M, Scheibel AB.
A quantitative dendritic analysis of Wernicke’s area in humans. II. Gender, hemispheric, and environmental factors.
J Comp Neurol. 1993 Jan 1;327(1):97-111.

Jurdak N, Lichtenstein AH, Kanarek RB.
Diet-induced obesity and spatial cognition in young male rats.
Nutr Neurosci. 2008 Apr;11(2):48-54.

Kosari S, Badoer E, Nguyen JC, Killcross AS, Jenkins TA.
Effect of western and high fat diets on memory and cholinergic measures in the rat.
Behav Brain Res. 2012 Nov 1;235(1):98-103. Epub 2012 Jul 20.

Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR, Havlik RJ.
Midlife blood pressure and dementia: the Honolulu-Asia aging study.
Neurobiol Aging. 2000 Jan-Feb;21(1):49-55.

Mark P. Mattson
The Impact of Dietary Energy Intake on Cognitive Aging
Front Aging Neurosci. 2010; 2: 5.

Messier C, Whately K, Liang J, Du L, Puissant D.
The effects of a high-fat, high-fructose, and combination diet on learning, weight, and glucose regulation in C57BL/6 mice.
Behav Brain Res. 2007 Mar 12;178(1):139-45. Epub 2006 Dec 17.

Mielke JG, Nicolitch K, Avellaneda V, Earlam K, Ahuja T, Mealing G, Messier C.
Longitudinal study of the effects of a high-fat diet on glucose regulation, hippocampal function, and cerebral insulin sensitivity in C57BL/6 mice.
Behav Brain Res. 2006 Dec 15;175(2):374-82. Epub 2006 Nov 1.

Molteni R, Barnard RJ, Ying Z, Roberts CK, Gómez-Pinilla F.
A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning.
Neuroscience. 2002;112(4):803-14.

Nilsson LG, Nilsson E.
Overweight and cognition.
Scand J Psychol. 2009 Dec;50(6):660-7.

Sabia S, Kivimaki M, Shipley MJ, Marmot MG, Singh-Manoux A.
Body mass index over the adult life course and cognition in late midlife: the Whitehall II Cohort Study.
Am J Clin Nutr. 2009 Feb;89(2):601-7. Epub 2008 Dec 10.

Valladolid-Acebes I, Stucchi P, Cano V, Fernández-Alfonso MS, Merino B, Gil-Ortega M, Fole A, Morales L, Ruiz-Gayo M, Del Olmo N.
High-fat diets impair spatial learning in the radial-arm maze in mice.
Neurobiol Learn Mem. 2011 Jan;95(1):80-5. Epub 2010 Nov 17.

van Praag H.
Exercise and the brain: something to chew on.
Trends Neurosci. 2009 May;32(5):283-90. Epub 2009 Apr 6.

Wu A, Molteni R, Ying Z, Gomez-Pinilla F.
A saturated-fat diet aggravates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain-derived neurotrophic factor.
Neuroscience. 2003;119(2):365-75.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Tuning In Your ADD/ADHD Child

tv-head-childAll of us know children who have a hard time staying still, who find it difficult to listen, who can’t follow directions no matter how many times you present them, and who occasionally blurt out comments at the most inopportune times. Often the criticism is poorly aimed. Are they just being kids, or could they be suffering from attention deficit disorder or attention deficit hyperactivity disorder?  ADD/ADHD can make it difficult for a person to inhibit his spontaneity. The diagnosis is not a simple one, and too often relies on nothing but subjective reports from school personnel and parents, leading to a prescription pad resolution. A complete examination is required for diagnosis. Have there been any sudden life changes, such as divorce, moving, death in the family, or entering a new school? Have thyroid and sleep problems been considered? How about anxiety or depression? Could there be heavy metal toxicity or other toxic exposure?

Some kids with ADD are hyperactive, but not all. Some have a physiological reason, some don’t. Many are able to pay close attention to things they like, while others get bored quickly. Some are impulsive or quick-tempered. Those who seem disobedient may not be so intentionally. Whether they outgrow this or not is anyone’s guess; there are plenty of adults with ADD/ADHD.  As often as drugs are prescribed, they might not be the best option for you or your child. At one end of the spectrum, there are the hyperactive kids; at the other end are the quiet dreamers who stare off into space. Bad parenting is not an issue, but effective parenting strategies can go a long way to correct problems.

One theory of ADD/ADHD has to do with a person’s executive function, which involves the cognitive processes needed to organize thoughts and actions, to prioritize tasks, to manage time efficiently, and to make decisions. Looking at this list, we might know more people with executive dysfunction than we thought, especially when it comes to situations that require the control of habitual responses or of resisting temptations. Occasionally a parent hears that his child is a joy in the classroom, making the parent wonder why that doesn’t hold true at home. More often, however, the parent hears the opposite. In school, the teacher’s strategies to manage executive function problems might include inhibition, organization of materials, peer tutoring and other student-friendly approaches. Parent strategies often stop at inhibition, others being clouded by frustration. Weakness in executive function may not be characteristic of all cases of ADD/ADHD, but appear to be one important component of the disorder (Willcutt, 2005).  Adults with frontal lobe damage exhibit similar behaviors as children suspected of having the ADD/ADHD spectrum, leading some researchers to associate the physiological dysfunction while implicating the catecholamine neurotransmitters that respond to the stressors that arouse fight or flight (Faraonea, 1998).

Have you ever heard static on your radio or seen a snowy picture on the TV? That kind of interference in a child’s brain can jostle the connections. You might be able to tune out extraneous input and focus on what has your interest, like Sunday’s football game, but kids can’t always do that because, first of all, their brains are far from being completely wired and, second of all, they might have a few aberrant neurons. Multiple, simultaneous stimuli compete for neural attention, whether visual or auditory in the case of formal education. It requires purposive attention to separate stimuli and to focus on an assigned task. Therefore, goals need to be announced prior to a task and motivation needs to be stirred. The first part is easy; the second, not. Even in the presence of imminent reward, children may be hard to motivate. Negative feedback or punishment is futile (Stevens, 2012) (Crone, 2003). In some instances there is a need for family counseling, especially where cognitive disorders appear to have a heritable nature.  Attendant conduct disorders (Toupin, 2000) can amplify and become legitimate societal concerns. Socioeconomic status may or may not be involved, although attention disorders may interfere with economic wherewithal, present and future. This may co-occur with food insecurity, in which case nutritional deficit plays a role in ADD/ADHD, where even subtle nutritional irregularities can affect attention and motor behavior (Conners, 1982).

It has been suggested that children of lower socioeconomic status who are academically and behaviorally challenged be supplemented with micronutrients and essential fatty acids to learn if positive changes in cognition, learning and behavior occur, for such effect has been seen in developed and developing societies (Frensham, 2012). No reason was given for targeting this population. Since many educators have had remarkable social and academic interactions with this group, this is curious. Although the cause of ADD/ADHD has not been absolutely identified, its link to vitamin/mineral/fatty acid deficiencies has been proposed. Zinc, iron, magnesium and iodine, and the long-chain polyunsaturated fats may have a profound impact on the development and aggravation of ADD/ADHD symptoms (Konikowska, 2012). The fact is that all of us should keep an eye on levels of these nutrients (Milne, 2000) (Fuchs, 2002).

It has been established that zinc is a co-factor in more than a hundred enzymes, including those that metabolize carbohydrates, prostaglandins and nucleic acids. It has a striking effect on neurotransmission, as well, and may be factored in hyperkinetic disorders, especially noting that children diagnosed with ADD/ADHD suffer from low levels. Low zinc values may point to other nutrient deficits, such as outright malnutrition.  Feasting on bags of snacks and sweets may fill an empty belly, but doesn’t answer physiological needs despite the low cost. Maternal habits that increase exposure to additives, alcohol and smoking during pregnancy are other factors to consider (Dodig-Curkovic, 2009). Magnesium is part of more than three enzymes, and its shortfall is conspicuous in ADD/ADHD individuals. That many youngsters avoid a wide range of vegetables, limiting themselves to corn and French fries, helps to explain this.  Supplementation with these minerals has brought positive outcomes (Starobrat-Hermelin, 1997, 1998) (Kozielec, 1997).

Whether ADD/ADHD will pervade a child’s life or not is undetermined. Many have outgrown the disorder, or at least have matured to the point of controlling the outward signs. Because mature gustatory sense admits a variety of plants into the diet, this alone might make a difference. Being proactive matters and introducing a child to one concept, task or image at a time can make a considerable difference in forming concepts from percepts.

References

Arnold LE, Bozzolo H, Hollway J, Cook A, DiSilvestro RA, Bozzolo DR, Crowl L, Ramadan Y, Williams C.
Serum zinc correlates with parent- and teacher- rated inattention in children with attention-deficit/hyperactivity disorder.
J Child Adolesc Psychopharmacol. 2005 Aug;15(4):628-36.

Carol Ballew, PhD; Sarah Kuester, MS, RD; Cathleen Gillespie
Beverage Choices Affect Adequacy of Children’s Nutrient Intakes
Arch Pediatr Adolesc Med. 2000;154:1148-1152

C.Keith Conners, Arthur G. Blouin
Nutritional effects on behavior of children
Journal of Psychiatric Research. Vol 17, Iss 2, 1982–1983, Pp 193–201

Eveline A. Crone, J. Richard Jennings, Maurits W. Van Der Molen
Sensitivity to interference and response contingencies in Attention-Deficit/Hyperactivity Disorder
Journal of Child Psychology and Psychiatry.  Vol 44, Iss 2, pp 214–226, Feb 2003

Dodig-Curković K, Dovhanj J, Curković M, Dodig-Radić J, Degmecić D.
The role of zinc in the treatment of hyperactivity disorder in children.
Acta Med Croatica. 2009 Oct;63(4):307-13.

Stephen V Faraonea,  Joseph Biederman
Neurobiology of attention-deficit hyperactivity disorder
Biological Psychiatry. Volume 44, Issue 10, 15 November 1998, Pages 951–958

Mariellen Fischer, Russell A. Barkley, Lori Smallish, Kenneth Fletcher
Executive Functioning in Hyperactive Children as Young Adults: Attention,
Inhibition, Response Perseveration, and the Impact of Comorbidity

DEVELOPMENTAL NEUROPSYCHOLOGY, 2005; 27(1): 107–133

Frensham LJ, Bryan J, Parletta N.
Influences of micronutrient and omega-3 fatty acid supplementation on cognition, learning, and behavior: methodological considerations and implications for children and adolescents in developed societies.
Nutr Rev. 2012 Oct;70(10):594-610. doi: 10.1111/j.1753-4887.2012.00516.x.

Nan Kathryn Fuchs, Ph.D.
Magnesium: A Key to Calcium Absorption
http://www.mgwater.com/calmagab.shtml

Koller, Harold P.
Visual processing and learning disorders
Current Opinion in Ophthalmology. September 2012 – Volume 23 – Issue 5 – p 377–383

Konikowska K, Regulska-Ilow B, Rózańska D.
The influence of components of diet on the symptoms of ADHD in children.
Rocz Panstw Zakl Hig. 2012;63(2):127-34.

Kozielec T, Starobrat-Hermelin B
Assessment of magnesium levels in children with attention deficit hyperactivity disorder (ADHD).
Magnes Res. 1997 Jun;10(2):143-8.

Mares D, McLuckie A, Schwartz M, Saini M.
Executive function impairments in children with attention-deficit hyperactivity disorder: do they differ between school and home environments?
Can J Psychiatry. 2007 Aug;52(8):527-34.

McMains S, Kastner S.
Interactions of top-down and bottom-up mechanisms in human visual cortex.
J Neurosci. 2011 Jan 12;31(2):587-97.

Millichap JG, Yee MM.
The diet factor in attention-deficit/hyperactivity disorder.
Pediatrics. 2012 Feb;129(2):330-7.

David B. Milne, PhD and Forrest H. Nielsen, PhD
The Interaction Between Dietary Fructose and Magnesium Adversely Affects Macromineral Homeostasis in Men
J Am Coll Nutr February 2000 vol. 19 no. 1 31-37

Sonuga-Barke EJ, Sergeant JA, Nigg J, Willcutt E.
Executive dysfunction and delay aversion in attention deficit hyperactivity disorder: nosologic and diagnostic implications.
Child Adolesc Psychiatr Clin N Am. 2008 Apr;17(2):367-84, ix.

Starobrat-Hermelin B, Kozielec T.
The effects of magnesium physiological supplementation on hyperactivity in children with attention deficit hyperactivity disorder (ADHD). Positive response to magnesium oral loading test.
Magnes Res. 1997 Jun;10(2):149-56.

Starobrat-Hermelin B.
The effect of deficiency of selected bioelements on hyperactivity in children with certain specified mental disorders.
Ann Acad Med Stetin. 1998;44:297-314.

Alexander A. Stevens, Leeza Maron, Joel T. Nigg, Desmond Cheung, Edward F. Ester,
Edward Awh
Increased Sensitivity to Perceptual Interference in Adults with Attention Deficit Hyperactivity Disorder
Journal of the International Neuropsychological Society (2012), 18, 1–10.

Jean Toupin, Michèle Déry, Robert Pauzé, Henri Mercier, Laurier Fortin
Cognitive and Familial Contributions to Conduct Disorder in Children
Journal of Child Psychology and Psychiatry. Vol 41, Iss 3, pp 333–344, March 2000

Willcutt EG, Doyle AE, Nigg JT, Faraone SV, Pennington BF.
Validity of the executive function theory of attention-deficit/hyperactivity disorder: a meta-analytic review.
Biol Psychiatry. 2005 Jun 1;57(11):1336-46

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.