Caffeine

Caffeine: Nutritional Jolt? by Dr. Chrisopher Jackson, PhD, DOM

A prominent drug found in the diets and cultural practices of populations throughout the world, caffeine is consumed by young and old alike, and marketing campaigns are now targeting younger populations directly (Turley et al., 2012). Along with any controversy over marketing efforts of caffeine-containing drinks toward children, there exists some controversy over the effects or perceived effects of caffeine among researchers. According to a study by Rogers et al. (2005), perceived stimulant effects of caffeine may be essentially the result of reversal of withdrawal from caffeine, rather than a beneficial performance improvement. A study by James, Gregg,, Kane, and Harte (2005), which monitored salivary caffeine levels to test compliance, appeared to agree with Rogers et al. (2005). One of this study's authors (James) had flagged, in a 1994 study, the inappropriate accounting for the consistent use of caffeine by most study participants in prior placebo-controlled studies of the potential performance and mood-altering effects of caffeine (James et al., 2005).

The study by Rogers et al. (2005) examined differential effects on fully withdrawn caffeine users (after 3 weeks of abstinence, also confirmed using salivary caffeine levels versus overnight withdrawn users). Rogers et al. (2005) found that overnight withdrawal impaired cognition, which returned to prior levels upon subsequent caffeine consumption. The same sort of improvement was not evident in fully withdrawn participants. However, caffeine increased jitteriness, reduced complaints of light-headedness, and improved clear-headed thinking in both fully and overnight withdrawn populations (Rogers et al., 2005). Aside from any performance improvements, additional problems with long-term caffeine consumption include osteoporosis, apathy, hyperstimulation of adrenal glands, and cardiac arrhythmia (Gummadi, Bhavya, & Ashok, 2012). In fact, greater all-cause mortality was seen in a study of 43,727 participants, particularly with men who consumed more than 4 cups of coffee per day (Liu et al., 2013).

Generally, cognitive performance and emotion studies have shown some of the effects of caffeine. James et al. (2005) included study of the differences in caffeine response between men and women. Memory tests showed better performance by women when both groups were rested, but performance that was poorer than men when the groups were sleep deprived (James et al., 2005). Caffeine's action on adenosine receptors to reduce inhibition of acetylcholine release (resulting in the presence of additional acetylcholine) may explain the memory improvements (Yang, Palmer, & de Wit, 2010). The negative effects of caffeine withdrawal included headaches, sleepiness, a perceived increased difficulty with cognitive challenges, and a reduction in the state of alertness (James et al., 2005; Rogers et al., 2005). Moods were improved slightly in both fully and overnight withdrawn populations.

Further studies regarding physical performance reveal some interesting results as well. Enhanced capacity for intense physical performance (ergogenicity) has been demonstrated following administration of caffeine (Duncan, Taylor, & Lyons, 2012). Essentially, this particular study showed a reduction of symptoms of fatigue after exercise that was of high intensity. Comparing the effects based on gender, Turley et al. (2012) reported that the blood pressure of boys and men was higher under the administration of 5mg/kg of caffeine. In adults, mean and peak power were significantly higher under administration of either 2.5 or 5.0 mg/kg of caffeine (Turley et al., 2012). According to Astorino, Terzi, Roberson, and Burnett (2011), muscle performance may improve with caffeine intake, whereas no amelioration of leg pain levels was seen. There is some controversy over the effects and levels of the internal stressors of the body (adrenal hormones). The study by Yang et al. (2010) suggests some direct negatives of elevated caffeine consumption, such as increased risk of myocardial infarction (heart attack), possibly due to elevation of catecholamine production. Yet, a study by Paton, Lowe, and Irvine (2010) of cyclists engaged in high intensity intermittent sprinting indicated enhancement of muscle performance, strength, and development with 240 mg caffeine administration. The study suggests that caffeine raises testosterone and lowers cortisol, while slowing the rate of development of fatigue (Paton et al., 2010). Note that all of the study participants received the same quantity of caffeine rather than a weight-proportioned dosage, possibly affecting the accuracy of corresponding physiological variations. Also, none of these studies addressed the possibility of a reverse withdrawal effect. An interesting point made by James et al. (2005) was that smoking speeds the elimination of caffeine, whereas contraceptives lengthen the time to elimination. According to James et al. (2005), without the influence of contraceptives or nicotine, symptoms of withdrawal typically appear 12 to 16 hours after consumption and peak after 24 to 48 hours. Therefore, the timing of measurement could influence the results in studies of physical performance related to caffeine ingestion.

According to Koppelstaetter et al. (2010), excitation of brain neurons involved in attention and executive thought processes may be at the root of the action of caffeine. The affect of caffeine on neurotransmitters noradrenaline, dopamine, and acetylcholine may lead to this excitation and resultant cognitive processes (Koppelstaetter et al., 2010). Yet, according to Yang et al. (2010), variations in reactions to caffeine may be influenced by genetic variations, such as polymorphisms in adenosine receptors, and ethnicity, as found in Caucasian metabolization of caffeine, which takes place at a faster rate than in Asians and Africans. Additionally, specific genetic predispositions may influence likelihood of dependency, withdrawal symptoms, insomnia or sleep disturbances, and anxiety, independent of any other addicitve predispositions. However, the choice of food source for the caffeine is somewhat culturally dependent, and may be influenced by the amount of caffeine in each of the food sources - tea, coffee, energy drinks, sodas, and chocolate (Yang et al., 2010).

Other combinations with caffeine are important as well. According to Sünram-Lea, Owen-Lynch, Robinson, Jones, and Hu (2012), the combination of glucose and caffeine may be of some benefit under stresssful conditions. Reduction in cortisol production and improvement in cognition were demonstrated when glucose was administered following a stressor (as opposed to prior to stressor exposure which has been shown to increase cortisol production). Caffeine mildly increased cortisol after stress. However, the presence of amino acid L-theanine in tea may offset the caffeine, since tea decreased cortisol response after stress (Sünram-Lea et al., 2012). It should be noted that the cyclical nature of cortisol (a factor in the circadian rhythm) could have affected the levels obtained, as well as response sensitivity. Also, the possibility of reversal of withdrawal symptoms was not addressed in this study.

Given the effects of caffeine, particularly the negative effects, other options could be examined. Decaffeination would be a viable and possibly preferable option for many who would like to consume the foods that typically contain caffeine. The preference would be for a process that accomplishes this function naturally and without toxic by-products (Gummadi et al., 2012). According to Gummadi et al. (2012), the typical chemical processes for decaffeination are not specific to caffeine, and create environmentally problematic by-products. One particular alternative to this form of decaffeination is microbial degradation, which is specific to caffeine, produces useful by-products theophylline and theobromine, and does not create the harmful by-products (Gummadi et al., 2012).

Another option would be to use a caffeine substitute. As with caffeine (due to withdrawal or otherwise), the herb Rhodiola rosea has been shown to improve athletic performance (enhancing ergogenicity), reduce fatigue, and improve cognition (Lee, Kuo, Liou, & Chien, 2009). All of this makes Rhodiola rosea a viable substitute for caffeine, especially since it is available as a tea. However, similar to caffeine again, Rhodiola rosea side-effects may be experienced, such as minor headaches, insomnia, and hypersalivation (Lee et al., 2009).

In summary, caffeine is simply a drug, and as with all drugs there are side-effects and withdrawal symptoms involved in the use or abuse of the drug. These effects include mood alterations, jitteriness, cardiovascular effects, possibility of myocardial infarction (heart attack), as well as muscular, and hormonal changes, particularly of a steroidal nature. Similar in many ways to anabolic steroids, and producing similar effects, the dangers of caffeine abuse are severe. Also, as is common with other drugs, addictive properties are evident. The addictive cycle is present due to the effects of withdrawal and its tendency to evoke a subsequent return to some form of the drug (chocolate, coffee, tea, cola, or energy drink). It is therefore advisable to examine further alternatives or to apply more stringent controls or medical oversight to the use of the drug caffeine. When is the last time your doctor asked you if you or your child drank caffeinated drinks? The studies examined herein would suggest that it would be wise to make this a standard question for every patient.

 

Copyright 2014 by Dr. Christopher Jackson, PhD, DOM

References

Astorino, T. A., Terzi, M. N., Roberson, D. W., & Burnett, T. R. (2011). Effect of caffeine intake on pain perception during high-intensity exercise. International Journal of Sport Nutrition & Exercise Metabolism, 21(1), 27-32.

Duncan, M. J., Taylor, S., & Lyons, M. (2012). The effect of caffeine ingestion on field hockey skill performance following physical fatigue. Research in Sports Medicine, 20(1), 25-36.

Gummadi, S., Bhavya, B., & Ashok, N. (2012). Physiology, biochemistry and possible applications of microbial caffeine degradation. Applied Microbiology and Biotechnology, 93(2), 545-554. doi:10.1007/s00253-011-3737-x

Ishaque, S., Shamseer, L., Bukutu, C., & Vohra, S. (2012). Rhodiola rosea for physical and mental fatigue: a systematic review. BMC Complementary And Alternative Medicine, 1270. doi:10.1186/1472-6882-12-70

James, J., Gregg, M., Kane, M., & Harte, F. (2005). Dietary caffeine, performance and mood: enhancing and restorative effects after controlling for withdrawal reversal. Neuropsychobiology, 52(1), 1-10.

Juliano, L. M., Evatt, D. P., Richards, B. D., & Griffiths, R. R. (2012). Characterization of individuals seeking treatment for caffeine dependence. Psychology Of Addictive Behaviors, 26(4), 948-954. doi:10.1037/a0027246

Koppelstaetter, F., Poeppel, T., Siedentopf, C., Ischebeck, A., Kolbitsch, C., Mottaghy, F., & ... Krause, B. (2010). Caffeine and cognition in functional magnetic resonance imaging. Journal of Alzheimer's Disease: JAD, 20 Suppl 1S71-S84. doi:10.3233/JAD-2010-1417

Lee, F., Kuo, T., Liou, S., & Chien, C. (2009). Chronic Rhodiola rosea extract supplementation enforces exhaustive swimming tolerance. The American Journal Of Chinese Medicine, 37(3), 557-572.

Lien, L., Lien, N., Heyerdahl, S., Thoresen, M., & Bjertness, E. (2006). Consumption of soft drinks and hyperactivity, mental distress, and conduct problems among adolescents in Oslo, Norway. American Journal of Public Health, 96(10), 1815-1820.

Liu, J., Sui, X., Lavie, C., Hebert, J., Earnest, C., Zhang, J., & Blair, S. (2013). Association of coffee consumption with all-cause and cardiovascular disease mortality. Mayo Clinic Proceedings. Mayo Clinic, 88(10), 1066-1074. doi:10.1016/j.mayocp.2013.06.020

Paton, C., Lowe, T., & Irvine, A. (2010). Caffeinated chewing gum increases repeated sprint performance and augments increases in testosterone in competitive cyclists. European Journal of Applied Physiology, 110(6), 1243-1250. doi:10.1007/s00421-010-1620-6

Pettit, M. L., & DeBarr, K. A. (2011). Perceived stress, energy drink consumption, and academic performance among college students. Journal of American College Health, 59(5), 335-341.

Rogers, P., Heatherley, S., Hayward, R., Seers, H., Hill, J., & Kane, M. (2005). Effects of caffeine and caffeine withdrawal on mood and cognitive performance degraded by sleep restriction. Psychopharmacology, 179(4), 742-752.

Sünram-Lea, S., Owen-Lynch, J., Robinson, S., Jones, E., & Hu, H. (2012). The effect of energy drinks on cortisol levels, cognition and mood during a fire-fighting exercise. Psychopharmacology, 219(1), 83-97. doi:10.1007/s00213-011-2379-0

Turley, K. R., Rivas, J. D., Townsend, J. R., Morton, A. B., Kosarek, J. W., & Cullum, M. G. (2012). Effects of Caffeine on Anaerobic Exercise in Boys. Pediatric Exercise Science, 24(2), 210-219.

Yang, A., Palmer, A., & de Wit, H. (2010). Genetics of caffeine consumption and responses to caffeine. Psychopharmacology, 211(3), 245-257. doi:10.1007/s00213-010-1900-1 

Weight Loss

Weight Loss and Good Health: Not a Simple Matter Any More

April 8, 2015, by Dr. Chris Jackson, DOM, PhD Natural Health, PhD-c Behavioral Medicine

It once was enough to eat a balanced, calorie-restricted diet and exercise regularly. No longer. The U.S. obesity rate for children age 6 to 11 has tripled over the last 30 years (6) and in Canada the rate for adolescents age 12 to 17 is approximately 29% (4). Far from balanced, at least one fast food meal is consumed every two days by approximately 37% of the U.S. population (3). Unfortunately, the trend starts early in life, since approximately three quarters of the U.S. population of teenagers (age 11 to 18) consume fast food for at least one meal per week (3). This is serious, since issues such as diabetes, asthma, sleep apnea, and poor academic performance, as well as poor emotional development, all have been linked to obesity in childhood and adolescence (8). Yet, elementary and middle schools throughout the U.S. offer cafeteria menus based on older nutritional standards and `a la carte items with very limited nutritional content, often containing pesticides and additives (1).

Not included in standard nutrition labeling, additives, antibiotics, pesticides, nitrates, heavy metals, and endocrine disruptors all affect the weight and health of our population. These can seriously affect hormones, cancer development, cognition, and thyroid function, thereby resulting in more weight issues (5). In addition to their contributions to obesity levels, endocrine disruptors add to our toxic loads, thereby challenging our immune systems. They can lead to hormonal imbalances, early puberty, and difficult female cycles (7). Endocrine disruptors also create the potential for development of other hormonally-related disorders, including endometriosis, ovarian cysts, fibrocystic breasts, and prominent types of cancers.

By avoiding fast food, additives, and sources of endocrine disruptors, better weight and better general health can be attained. Read labels! The word NATURAL does NOT mean ORGANIC, which means that items labeled NATURAL may still contain pesticides. It's pretty difficult to totally avoid endocrine disruptors, but here are some basic suggestions that can help. Don't leave plastic drink bottles in hot cars or just use glass-jarred drinks. Read labels to see if packaging is BPA free (it will say so if it is), including canned foods. Avoid farm-raised salmon (wild caught is better) and tilapia, and avoid wild game fish (shark, tile fish, king mackerel, and swordfish) which may be high in mercury (another endocrine disruptor and a toxic heavy metal). Reject skin care products with parabens. Avoid pastries and baked goods, which in addition to parabens, often contain bromates/bromides, chlorine, and fluoride (from tap water) that can lower your metabolism. As you can see, there is much more to weight loss, and good health, than eating a balanced meal!

Men's Health

Hey gentlemen. Here's the scoop: Things change as you age! For some more than others.

 

Testosterone will likely decline, and this hormone is important for more than just functionality, including heart and general muscle strength. Also important are Co-enzyme Q10 (best taken as Ubiquinol) and B12 (best taken as methylcobalamin). These both tend to be reduced by taking statin drugs for your cholesterol. Yep, taking a drug to reduce cholesterol to reduce potential for heart problems can damage your muscles including your heart! See anything wrong with this scenario? So, if you're taking a statin, you should look into taking these vitamins as supplements. Ask your doc about this!

 

In addition, estrogen, that's right - the “female hormone” estrogen, will likely increase. This is because of a little enzyme, known as the aromatase enzyme, that acts over time in the background quietly converting testosterone to estrogen. Can these changes have negative consequences? Absolutely!

Does this mean some things wont be working as well? Maybe. That's right, maybe!

It depends a lot on you. Are you taking prescription drugs that affect your ability to perform? Some may have negative effects. Some may improve things for a little while. Are they addressing the root cause? NOT.

 

Are there other ways of handling your health issues? Most likely! Do you take blood pressure meds? Antidepressants? Smoke a little something on the side? How about the standard cigarettes? Drinking much alcohol? These and many other drugs can affect your manhood, and possibly your drive (libido).

How can you improve your lot in life? Well, that increase in estrogen, along with the decrease in testosterone, are not at all inevitable if you address the issues soon enough.

 

First of all, you can drink green tea. I know, it's all the rage. Well, with good reason! Green tea is a natural aromatase enzyme inhibitor. Yep, it helps to keep that nasty enzyme at bay, allowing you to keep more of your testosterone and produce less estrogen. This is also helpful to prevent cancers including breast and prostate cancer, and yes, men get breast cancer too!

 

Try to use as much of the naturally decaffeinated version as feasible to avoid raising blood pressure – despite Dr. Oz saying caffeine is OK if you have hypertension - Duh! Also, watch it with natural enhancing substances that can raise blood pressure, like Yohimbe. Best to seek qualified help with expertise in the method you choose before embarking on any path.

 

Believe me, there are many other facets to approaching these issue, but let's not keep harping on the same core subject for the whole article, shall we? What about the prostate? Well, you may have heard of saw palmetto. That's right. It can help with a condition known as benign prostatic hypertrophy (BPH), which is enlargement of the prostate that can take place over time, just like the hormonal changes. And you thought only women had hormonal issues! Think again. BPH can cause urinary urgency and constriction of the parts in the groin area. Saw palmetto contains a substance known as pygeum africanum. Other food items contain this same substance. A couple of my favorites are pistachio nuts and pumpkin seeds. So remember your Ps for prostate – saw palmetto, pumpkin seeds, and pistachios.

 

To wrap it up, there are many ways to change your lot in life. You can accept “the inevitable” - Crock of !#@$% or you can improve your health naturally, in all areas. Watch for more articles in the future and listen to A Path to Wellness radio on WSPF-DB.com Thursdays at noon (or listen to podcasts).

 

(Note: this article is not intending to treat, cure, or prevent disease, and these statements have not been evaluated by the FDA).. yadah yadah. Dr. Chris Jackson. Join me on … A Path to Wellness!

Malnutrition and Behavior

Effects of Undernutrition and Malnutrition on Behavior by Dr. Chris Jackson, PhD, DOM

Malnutrition during fetal development often results in malnutrition as an infant and during later developmental stages, including adolescence and adulthood. A woman who is malnourished is likely to yield a malnourished child, possibly with diminished brain development, and generally, a failure to thrive. Failure to thrive, more common to poorer populations, may lead to decreased growth and a resulting lag in cognitive development that reduces achievement levels throughout life (Cole & Lanham, 2011). In a cyclical fashion, psychological conditions, such as depression, anxiety, obsessive-compulsive disorder (OCD), or anorexia nervosa, may also lead to malnutrition, further developing into additional psychological disorders, especially in the elderly (Clarke, Wahlqvist, Rassias, & Strauss, 1999; Cole & Lanham, 2011). Overnutrition, undernutrition or malnutrition may result in mineral or vitamin deficiencies or excesses. This result may be due to poor food choices, a lack of sufficient nutritious foods, malabsorption of the foods due to metabolic disorders, or the lack or excess of supplementation, all of which may be involved in the etiology of psychological disorders (Cole & Lanham, 2011).

Deficiency of the micronutrient element iodine is of broad importance. Iodine is an important component of thyroid hormone, thereby affecting hormone levels in the body and metabolism of all of the important nutrients. Iodine deficiency in early childhood may lead to measurably diminished intellectual abilities (lower IQ), partly due an early role in brain development. Also, the deficiency may lead to thyroid dysfunction affecting nutrient and sugar metabolization, resulting in cognitive impairment. Additionally, iodine deficiency may be involved in the development of attention deficit hyperactivity disorder (ADHD) (Benton, 2008).

Deficiencies of minerals, particularly iron, zinc, selenium, magnesium, and copper may affect brain development, structure and function. Iron deficiency may result from excess zinc, reducing the number of neurons, thereby leading to memory problems and reduced ability to focus (Huss, Völp, & Stauss-Grabo, 2010). Magnesium and zinc deficiencies may also exacerbate the symptoms of attention deficit hyperactivity disorder (Huss et al., 2010). Deficient magnesium may decrease serotonin levels, reduce responsiveness to serotonin, reduce GABA levels, and affect the levels of stimulating neurotransmitters noradrenaline (norepinephrine) and dopamine, possibly leading to depression, anxiety, or sleep disorders (Lakhan & Vieira, 2008). According to Lakhan and Vieira (2008), excess vanadium may lead to bipolar disorder (BPD).

Vitamin deficiencies may also lead to psychological conditions. Vitamin A is important for neuron differentiation, and may be a key nutrient for proper memory function. Vitamin A deficiency is found to be more common in the poor and in the black population (Benton, 2008). Aside from excess vanadium, BPD may also evolve from deficiencies in B vitamins, specifically B12 or folate, or vitamin C. Vitamin C deficiency may contribute to excess vanadium, leading to BPD (Lakhan & Vieira, 2008). Deficiency of B12 can result in demyelination in early life and a lack of proper neurological development through adolescence, resulting in lagging cognitive development and depressive symptoms, possibly due to reduced methylation resulting in elevated homocysteine and reduced S-adenosyl-L-methionine (Black, 2008). However, the correlation between deficiencies of B vitamins and depression were not confirmed in a study by Kamphuis, Geerlings, Grobbee, and Kromhout (2008). According to Jorde, Sneve, Figenschau, Svartberg, and Waterloo (2008), depression can also result from deficient vitamin D levels. Additionally, McGrath (2010) suggests that schizophrenia may result from vitamin D deficiency (hypovitaminosis D), although this is not well-researched. Receptors for vitamin D are prominent in the brain, located particularly in the substantia nigra and hypothalamus, and functionally important to the hypothalamus-pituitary-adrenal (HPA) axis (Gracious, Finucane, Friedman-Campbell, Messing, & Parkhurst, 2012)..

Malnutrition or undernutrition may result in protein deficiency, leading to deficiencies of the amino acids, which may result in psychological disorders. According to Lakhan and Vieira (2008), deficiency of tryptophan can lead to serotonin deficiency, and tyrosine deficiency can lead to dopamine or noradrenaline (norepinephrine) deficiencies, possibly leading to depression, anxiety, or sleep disorders. Additionally, tryptophan deficiency, as well as deficiency of amino acid glycine, have been linked to schizophrenia. Deficiency of taurine can allow a build-up of excess acetylcholine. Interestingly, the excess acetylcholine may be helpful for Alzheimer's patients and those with memory issues, yet be harmful for individuals with BPD who may be sensitive to acetylcholine, leading to mania (Lakhan & Vieira, 2008).

Omega 3, 6, and 9 oils are important as well, especially to the development of the brain and neurological systems. In the case of deficiencies of omega 3 oil docosahexaenoic acid (DHA), a component of the cell membranes of neurons, aggressiveness may be elevated, and memory and learning may be negatively affected (Huss et al., 2010; Peet & Stokes, 2005). Deficiency of omega 3 oil eicosapentaenoic acid (EPA), a modulator of neuronal activity, may exacerbate the symptoms of schizophrenia. This inherent deficiency may be due to abnormal phospholipid metabolism, the lack of anti-inflammatory activity, or the lack of inhibition of phospholipase A2 in individuals with schizophrenia, and may also lead to depression or anxiety (Lakhan & Vieira, 2008; Peet & Stokes, 2005). Omega 3 and 6 deficiencies may also exacerbate the symptoms of BPD, postnatal depression, borderline personality disorder, and ADHD, including hyperactivity, impulsivity, sleep problems, emotional, and behavioral problems (Huss et al., 2010; Peet & Stokes, 2005).

As discussed, there are many nutritional deficiencies and some excesses that may be linked etiologically to psychological disorders, including OCD, BPD, schizophrenia, borderline personality disorder, depression, ADHD, anxiety, and others. Further study in all of these areas would be helpful in determining the full extent of causality and biologically required levels for treatment. Such research could help to advance the field of orthomolecular psychiatry and to reduce the widespread application of problematic antipsychotic drugs and their side-effects.

 

Copyright 2014 by Dr. Christopher Jackson, PhD, DOM

References

Atinmo, T., Mirmiran, P., Oyewole, O., Belahsen, R., & Serra-Majem, L. (2009). Breaking the poverty/malnutrition cycle in Africa and the Middle East. Nutrition Reviews, 67 Suppl 1S40-S46. doi:10.1111/j.1753-4887.2009.00158.x

Benton, D. (2008). Micronutrient status, cognition and behavioral problems in childhood. European Journal of Nutrition, 47 Suppl 338-50. doi:10.1007/s00394-008-3004-9

Black, M. (2008). Effects of vitamin B12 and folate deficiency on brain development in children. Food and Nutrition Bulletin, 29(2 Suppl), S126-S131.

Clarke, D., Wahlqvist, M., Rassias, C., & Strauss, B. (1999). Psychological factors in nutritional disorders of the elderly: part of the spectrum of eating disorders. The International Journal Of Eating Disorders, 25(3), 345-348.

Cole, S., & Lanham, J. (2011). Failure to thrive: an update. American Family Physician, 83(7), 829-834.

Gracious, B., Finucane, T., Friedman-Campbell, M., Messing, S., & Parkhurst, M. (2012). Vitamin D deficiency and psychotic features in mentally ill adolescents: a cross-sectional study. BMC Psychiatry, 1238. doi:10.1186/1471-244X-12-38

Huss, M., Völp, A., & Stauss-Grabo, M. (2010). Supplementation of polyunsaturated fatty acids, magnesium and zinc in children seeking medical advice for attention-deficit/hyperactivity problems - an observational cohort study. Lipids in Health and Disease, 9105. doi:10.1186/1476-511X-9-105

Jorde, R., Sneve, M., Figenschau, Y., Svartberg, J., & Waterloo, K. (2008). Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. Journal of Internal Medicine, 264(6), 599-609. doi:10.1111/j.1365-2796.2008.02008.x

Kamphuis, M., Geerlings, M., Grobbee, D., & Kromhout, D. (2008). Dietary intake of B(6-9-12) vitamins, serum homocysteine levels and their association with depressive symptoms: the Zutphen Elderly Study. European Journal of Clinical Nutrition, 62(8), 939-945.

Khor, G., & Misra, S. (2012). Micronutrient interventions on cognitive performance of children aged 5-15 years in developing countries. Asia Pacific Journal of Clinical Nutrition, 21(4), 476-486.

Lakhan, S., & Vieira, K. (2008). Nutritional therapies for mental disorders. Nutrition Journal, 71-8.

McGrath, J. (2010). Is it time to trial vitamin D supplements for the prevention of schizophrenia?. Acta Psychiatrica Scandinavica, 121(5), 321-324. doi:10.1111/j.1600-0447.2010.01551.x

Peet, M., & Stokes, C. (2005). Omega-3 Fatty Acids in the Treatment of Psychiatric Disorders. Drugs, 65(8), 1051-1059.

Nutrition for Aging

Nutritional Help with Aging by Dr. Christopher Jackson, PhD, DOM

Introduction

The conventional approach to treatment of disorders associated with aging tends to focus on treatment of symptoms, rather than correction of underlying causal factors. The issues of cognitive decline, Alzheimer's disease (Alzheimer's), and dementia are of prime importance in the elderly. As of 2010, the number of individuals afflicted with dementia was in excess of 24 million, and expected to double in 20 years (Fratiglioni, Mangialasche, & Chengxuan, 2010). Dementia is one of the more obvious characteristics of Alzheimer's, which is responsible for 60 to 70 percent of dementia cases according to Fratiglioni et al. (2010). However, dementia does not necessarily indicate that an individual has Alzheimer's, since vascular dementia is generally considered the second leading cause. Fratiglioni et al. (2010) suggested that a combination of the two they called mixed dementia may actually be the most common form at 53 percent of the cases of dementia.

By addressing the underlying causes, natural preventative solutions to treatment of the effects of aging could go a long way toward the reduction of both the personal and the public healthcare costs. These costs include the high costs of care and the drugs used conventionally for the treatment of dementia, Alzheimer's, and the cognitive decline that may occur with aging (Oremus & Aguilar, 2011). The following review will explore the underlying causal factors, as well as potential natural treatments for disorders associated with aging.

The Underlying Causes

Fratiglioni et al. (2010) explored a range of hypotheses on the underlying causes of dementia and Alzheimer's through a nutritional filter. The authors correlated a combination of genetic (especially with a first degree relative with Alzheimer's), environmental, vascular (hypertension, cerebrovascular disease, heart disease, stroke, or diabetes), inflammatory, and psychosocial factors. Additionally, according to Fratiglioni et al. (2010), the chances of late-life dementia, Alzheimer's, and declining cognitive function increase as total cholesterol declines after midlife (inversely proportional), yet elevated cholesterol going into midlife also increases the likelihood of cognitive decline, Alzheimer's, and dementia late in life.

Folstein and Folstein (2010) referenced a study of the aging brain focused on nutrition and memory loss of 365 participants. The study filtered out participants who had been diagnosed with dementia. The evaluation of brain atrophy using MRI revealed a correlation with vascular degradation, suggesting the possibility that MRI technology could be used to evaluate nutritional treatment solutions (Folstein & Folstein, 2010).

In the elderly, malnutrition and weight loss may manifest as a loss of muscle mass (sarcopenia) correlated with dementia, but according to Faxén Irving (2003), which comes first (sarcopenia or dementia) is unclear. It is possible that the inability to recognize, taste, or prepare food, or even remember how to eat, may result in malnutrition and eventually sarcopenia (Faxén Irving, 2003). Chwang (2012) contended that elderly nutrition and diet may lead to deficiencies correlated to disorders such as Parkinson's, dysphagia (inability to swallow), sarcopenia, and dementia.

At least one of the mechanisms of damage for dementia and other forms of cognitive impairment, as well as neurological disorders, is oxidative damage produced by free radicals that strip electrons from molecules throughout the human body. The free radicals result from exposure of human beings to a plethora of environmental toxins, nutritional deficiencies resulting in a lack of antioxidants, and primarily from normal metabolic processes related to mitochondrial activity such as cellular respiration (particularly in the aging brain), damaging cell membrane lipids, DNA, and proteins in the brain and throughout the body (Daffner, 2010; Stough et al., 2012).

Another mechanism, when not functioning optimally, the process of methylation takes part in the creation of neurotransmitters, derivation of methionine from homocysteine, and production of cell membranes. Dao-Mei et al. (2010) studied 662 elderly participants, 57.1 percent women, and statistically confirmed a direct correlation between homocysteine levels and cognitive dysfunction. Cardiovascular function is also negatively affected by elevated homocysteine levels, which may cause inflammatory processes that lead to pathology when elevated (Dao-Mei et al., 2010; Jia, McNeill, & Avenell, 2008).

According to Kagawa (2012), telomeres are involved in additional mechanisms of damage through shortening and eventual programmed cell death (cellular senescence). Aging is established partly by the lengths of telomeres, the base material at the end of DNA (chromosomes) that is involved in cellular replication. Telomere length shortens over time with each cycle of replication, reducing mitochondrial activity with each cycle, until the material is gone and cell death occurs (Kagawa, 2012).

Several processes are important to proper neurological function and production of neurotransmitters. Such processes can be influenced by excesses or deficiencies of certain vitamins and minerals (micronutrients), as well as macronutrients, such as fatty acids and chains of amino acids that form proteins (Camardese et al., 2012). Thus, nutritional deficiencies or excesses can be contributors to the aging process, and nutritional substances may help to delay aging processes.

Antioxidant vitamins are involved in many processes in the human body. Neurons and cerebrospinal fluid contain high amounts of the important antioxidant ascorbic acid (vitamin C). Vitamin C is an essential cofactor in enzymatic processes, especially since human beings lack the ability to derive vitamin C from glucose due to the lack of enzyme gulonolactone oxidase (Bowman, 2012; Morris, 2009).

The process of methylation can be disrupted by a lack of methyl donors, particularly B vitamins such as methylcobalamin (B12), niacin (B3), and pyridoxine (B6) (Dao-Mei et al., 2010). Selhub, Troen, and Rosenberg (2010) also examined the associations between vitamins B6, folate (B9), and B12, homocysteine, and aging. The authors found that B vitamin deficiencies, and elevated homocysteine levels were each directly correlated with dementia, cognitive dysfunction, and Alzheimer's (Selhub et al., 2010). B12 deficiency is common among the elderly, as is the use of antacids such as proton pump inhibitors that are likely to cause B12 deficiency, according to a recent large-scale study by Lam, Schneider, Wei, and Corley (2013), worsening an already prevalent situation. The study of 25,956 B12 deficient individuals compared antacid use with 184,199 individuals without B12 deficiency and found that proton pump inhibitor use of greater than 2 years lead to a 65 percent increased likelihood of B12 deficiency, even greater with increased dosage.

Coenzyme Q10 (CoQ10) helps to energize every cell in the body and supports muscle function, including the heart (Challem, 2009). CoQ10 is also neuroprotective, particularly in the dopaminergic neurons (Chao, Leung, Wang, & Chang, 2012). According to Potgieter, Pretorius, and Pepper (2013), a secondary effect of the common use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) for hypercholesterolemia and other disorders is the reduction of CoQ10 levels, due to the effect of statins on mevalonate, a precursor to CoQ10 production. Genetic mutations can lead to a primary form of CoQ10 deficiency as well. CoQ10 is a cofactor in the electron transport chain in mitochondria, thereby affecting the energy level of the individual via adenosine triphosphate (ATP) production. Therefore, if an individual has a deficiency in CoQ10, energy levels suffer throughout the body, including the brain, skeletal muscles, and the heart. Additionally, a deficiency in tyrosine could lead to a CoQ10 deficiency since tyrosine is a precursor in the biosynthesis of CoQ10 (Potgieter et al., 2013).

Antioxidant minerals play important roles as well. The mineral selenium is an antioxidant mineral important to neuronal and cognitive function that also affects thyroid hormone levels. According to Torres-Vega, Pliego-Rivero, Otero-Ojeda, Gómez-Oliván, and Vieyra-Reyes (2012), high levels of selenium, zinc, and copper exist in the hippocampus. Iron deficiency can result from elevated zinc, leading to reduced neuronal branching and cognitive dysfunction. Iron is found in the dopamine centers of the brain, such as the substantia nigra, and in the oligodendrocytes, affecting the central nervous system (CNS). Cu levels positively affect dopamine beta hydroxylase activity, thereby also affecting neurotransmission in the CNS. Additionally, copper affects the synthesis of neuropeptides via peptidyl glycine a-amidating mono-oxygenase. Zinc blocks gamma-aminobutyric acid (GABA) receptors, affecting excitabiliy if elevated (Torres-Vega et al., 2012). Magnesium positively affects levels of dopamine, serotonin, GABA receptors, and catecholamines, possibly leading to mood fluctuations when deficient (Camardese et al., 2012).

Antioxidant enzymes are also quite important to cognitive and neuronal function, and use many minerals and vitamins as cofactors. According to Torres-Vega et al. (2012), iron is found in the enzymes tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase. Tyrosine hydroxylase and phenylalanine hydroxylase are involved in the production of catecholamines, dopamine production, and thyroid function. Tryptophan hydroxylase positively affects tryptophan production, a precursor to serotonin and melatonin. Zinc and copper promote superoxide dismutase activity (a powerful antioxidant) at the cellular level. Selenium is a co-factor of glutathione peroxidase, thioredoxin reductase, and iodothyronine deiodinase, the latter pulling iodide from thyroxine (T4), resulting in triiodothyronine (T3) hormone. T3 is the more active thyroid hormone for metabolic optimization, which also affects the absorption of glucose into the brain, supporting cognition. The CNS also depends on these antioxidant enzymes to protect neurons from antioxidant damage (Torres-Vega et al., 2012).

According to Lakhan and Vieira (2008), fatty acids are also important to neurological development, maintaining a balanced mood, and general cognitive and synaptic function (and prevention of decline). The most efficacious oils for these purposes are omega 3 polyunsaturated fatty acids (found primarily in fish oil). The omega 3 oils include docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which is also a precursor to DHA. González, Huerta, Fernández, Patterson, and Lasheras (2010), was a study of 177 elderly women and 127 elderly men who were institutionalized and mostly aged in the 70s. The study examined the correlation between cognitive performance and intake of fatty acids. DHA and EPA levels were found to be directly correlated with cognitive function. Morris (2009) correlated greater frequency of Alzheimer's with higher levels of saturated fats, yet elevated DHA and high vitamin E amounts tended to be associated with less frequent occurrence of Alzheimer's. The level of aggressive behavior, according to Alfonso and Alberto (2005), and depression, according to Lakhan and Vieira (2008), were reduced when high density lipoprotein (HDL) levels (the so-called good cholesterol), were elevated, which resulted from increased consumption of Omega 3 fatty acids.

Faxén Irving (2003) highlighted the importance of differentiating between choices of fats, pointing out that a negative effect was seen on cognition along with a worsening of dementia with high fat intake, yet when omega 3 was the fat of choice the result was a very positive anti-inflammatory effect reducing the chances of dementia onset. Fratiglioni et al. (2010) also pointed to a lower risk of dementia, specifically at higher levels of omega 3 fatty acid EPA. Omega 9 monounsaturated oils (most prominently olive oil) are important for long-term health as well, and are an essential component of the Mediterranean diet. However, inflammatory conditions, cognitive decline, and neurological dysfunction are often the result of the overabundance of omega 6 fatty acids in the western diet (Daffner, 2010; Jia et al., 2008; Karr, Alexander, & Winningham, 2011; Morris, 2009).

Treating the Cause

Telomere shortening is an effect that can be delayed through caloric restriction, thereby lengthening lifespan (Kagawa, 2012). In addition to delaying the shortening of telomeres, Bernardes de Jesus et al. (2011) demonstrated in mice and Wang, Zhang, Sun, Liu, and Tong (2010) showed in human female lung tissue that telomeres could be lengthened when critically short and DNA damage could be repaired. Therefore, an essential element of aging could be reversed. The substances studied were extracts of the herb Astragalus membranaceus, also known in traditional Chinese herbal medicine as Huang Qi (Bernardes de Jesus et al., 2011; Wang et al., 2010).

Bowman (2012) showed that proper diet and nutritional intake could possibly delay the onset of Alzheimer's. According to Fratiglioni et al. (2010), the risk of cognitive impairment, dementia, and Alzheimer's were inversely correlated with elevated vegetable and fruit consumption. Viewing this more broadly, an inverse association was found with adherence to a Mediterranean diet, including high legume, vegetable, fruit, and fish intake, as well as a low beef and poultry intake (Fratiglioni et al., 2010).

Vitamins and minerals that may help to reduce the effects of aging are functionally related to the processes involved in aging. Specifically, antioxidants are naturally occuring vitamins and minerals that donate electrons, essentially helping to repair oxidative damage that contributes to the aging process (Lakhan & Vieira, 2008). When vitamin C is combined with vitamin E, cognitive function can be improved due to effective repair of the fatty membranes of vascular cells and a resultant reduction in the level of inflammation throughout the body, and particularly the brain (Bowman, 2012; Morris, 2009). Additionally, dementia may be delayed through the kinds of extracurricular activities that include physical, social, and mental components (Fratiglioni et al., 2010). Chao et al. (2012) agreed that some degree of neuroprotection exists with vitamin E supplementation, as well as the combination of vitamins C and E, but indicated differing views on the effectiveness of vitamin C alone.

According to Challem (2009), antioxidant CoQ10 assists longevity by helping to prevent and treat disorders including cardiological and immune system issues. CoQ10 also helps to keep energy levels and cognition optimal. Acetyl-l-carnitine (1 gram daily) in combination with CoQ10, alpha lipoic acid (200mg daily), and vitamin C (1 gram daily), helps to increase energy production, cognitive acuity, and muscle mass. Vitamins thiamin (B1), riboflavin (B2), and B3 help CoQ10 and carnitine to improve energy production. Additionally, B12 and B9, combine with B2 and B3 to improve gene synthesis and repair (Challem, 2009). A safe limit for CoQ10 supplementation of 1200 mg per day has been suggested by Potgieter et al. (2013).

Other substances are of importance according to Chiu, Lalone, and Goble (2007), who examined the biochemical mechanisms of various alternative treatments for Alzheimer's disease and schizophrenia, particularly Huperzine A, an alkaloid extract from the Chinese moss Huperzia serrata. Huperzine A helps to modulate dopamine and noradrenaline levels via neurotransmitter N-methyl-D-aspartic acid (NMDA), and inhibits the acetylcholinesterase enzyme, which dissolves unused quantities of neurotransmitter acetylcholine, leaving more available for use by the brain. Huperzine A did well in comparison with acetylcholinesterase inhibitor Aricept ( donepezil) in lab rat studies, and some human studies at 60 to 200 mcg doses. Huperzine A has the added benefit, versus Aricept, of NMDA modulation, which may have a neuroprotective effect against nerve death due to the activity of excitotoxins, such as flavor enhancer monosodium glutamate and artificial sweetener aspartame (Chiu et al., 2007).

Many other substances are of interest to improve upon or delay the effects of aging. According to Challem (2009), the potent antioxidant resveratrol can have the effect of increasing lifespan, at 100 to 200 mg per day. Resveratrol triggers the protective silent information regulator T1 (SIRT1) gene which prevents apoptosis through protein deacetylation and by binding directly to telomeres. Resveratrol also has blood sugar regulating properties, providing protection against diabetes and its sequela (Challem, 2009; Kagawa, 2012). Cat's claw (Uncaria tomentosa), a well-studied herb with antioxidant and antitumor effects (inducing apoptosis), also helps with DNA repair (Bacher et al., 2006; Challem 2009).

Other substances, such as proanthocyanidins aside from resveratrol, and curcuminoids (found in turmeric) help fight inflammatory conditions from cognitive to cancer to cardiovascular disease (Challem 2009; Stough et al., 2012). According to Sood et al. (2011), curcumin (the source of curcuminoids) helps to reduce inflammation in neurons. In this rat study the source of inflammation was aluminum and a small population was sampled, thus a larger human study of inflammatory responses with curcumin is suggested. Chao et al. (2012) attribute additional neuronal protection by curcumin to the restoration of glutathione.

Treatment through Intervention

Interventional programs could include nutritional training at assisted living facilities, which would address the elderly population directly, and could help to improve nutrition and diet, possibly preventing much of the cognitive decline seen in the aging populations. The training could also help to prevent further degradation of bones and joints or reduce the degree of osteoporosis seen in many elderly (Manios, Moschonis, Katsaroli, Grammatikaki, & Tanagra, 2007). Nutritional training of caregivers could help them to pass nutritional knowledge and benefit to the elderly, and improve their understanding of the needs of elderly patients. For the more isolated among the elderly population, a telephone intervention program could be developed to include counseling sessions to address the specific needs of each individual.

An interventional media campaign targeting the elderly population could be helpful in promoting healthy eating habits particularly beneficial to the elderly. Promoting increased consumption of antioxidant rich fruits and vegetables, as well as cold water fish rich in omega 3 fatty acids DHA and EPA, as well as vitamin D for bone and immune health along with promotion of the Mediterranean diet, could raise the level of awareness of nutritional needs, and make a difference in the incidence of dementia, Alzheimer's, and cognitive decline among the elderly (Brambila-Macias et al., 2011; Fratiglioni et al., 2010). Community involvement and participation by organizations supportive of the elderly, such as the American Association of Retired Persons (AARP), could help to ensure thorough implementation of the interventional programs, refresh elderly individuals whose memories might not be optimal, and expand upon the understanding and implementation of diet and nutrition improvements (Goode, Owen, Reeves, & Eakin, 2012).

Conclusion

There is certainly no shortage of substances that can affect the aging process. Most deficiencies of micro and macronutrients can be addressed through sufficient supplementation. B vitamin supplementation could help to bring down homocysteine levels, improve the methylation process, reduce inflammation, and improve cognitive function (Dao-Mei et al., 2010; Jia, McNeill, & Avenell, 2008). Supplementation with the specific precursors to cognition, such as choline to help synthesize the important neurotransmitter acetylcholine, could make the difference more significant. Huperzine A helps to keep the acetylcholine level up as well, improving cognitive function and memory. CoQ10 supports the energy factories in the body (mitochondria) and is important to the strength and structure of the skeletal muscles and the cardiovascular system. Vitamins C and E combine to maintain vascular cell walls and minimize inflammation, especially with the addition of turmeric (curcuminoids). A balance of minerals also helps to optimize neurotransmitter levels. Therefore, a good daily multivitamin/mineral is essential for the aging population, and can be enhanced by supportive extracts.

 

Copyright 2014 by Dr. Chrisopher Jackson, PhD, DOM

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Sensory Learning Dysfunction Casual Factors

Underlying Mechanisms of Developmental Disorders by Dr. Christopher Jackson, PhD, DOM (FL)

The specific mechanisms by which developmental disorders evolve pre- and post-natally range from high-level metabolic processes to low-level cellular processes. These processes may affect cerebellar, vestibular, auditory, or optical processing. Several studies have pursued the underlying causes of disorders of cerebellar function and related sensory learning deficits. Studies explore the effects of hypo- and hyperthyroidism, endocrine disruptor effects on brain development, and the similarity of endocrine disruptor effects to the effects of thyroid hormone.

Thyroid hormone, particularly triiodothyronine (T3), may be under-appreciated in the medical community for its role in brain development. Generally the realm of endocrinologists rather than neurologists or developmental specialists, thyroid hormone actually appears to be involved in many roles beyond standard metabolic functions. According to Anderson (2008), referencing over 180 studies, deficiency of thyroid hormone pre- or post-natally may result in dysfunctions, cellular changes, and molecular variations via regulation of gene transcription. These actions are accomplished via binding of thyroid hormone, particularly T3, with thyroid hormone receptors that subsequently bind with thyroid hormone response element DNA sequences. Thyroid hormone may also induce neurotrophin gene expression, thereby indirectly activating genes (Anderson, 2008). Thus, there are many aspects to the involvement of thyroid hormone on brain development, including several influences on the cerebellum.

Abnormal cerebellar development may be commonly induced by perinatal hypothyroidism leading to reduced dendritic proliferation. This early hypothyroidism also may lead to reduced development of Purkinje cells and a reduction, and delay in myelination. These abnormalities may lead to impaired voluntary motor activity or strabismus, and may be avoided or reversed to some extent if thyroid hormone is replaced quickly enough after birth (Anderson, 2008). Koibuchi (2009) examined additional mechanisms via which thyroid hormones may affect brain development, particularly the cerebellum, including monocarboxylate transporter 8 (MCT8). The study explored the activity of various deiodinases in the conversion and breakdown of thyroid hormones within neurologic pathways, including conversion of thyroxine (T4) to active thyroid hormone T3 in astrocytes, tanycytes, and transfer to oligodendrocytes. Such molecular and neurological mechanisms appear to contribute significantly to the origins of developmental delays.

Other molecular and neurological mechanisms, related to thyroid dysfunction, have been studied to help isolate underlying causal factors for cerebellar developmental disorders. Li, Post, Koibuchi, and Sajdel-Sulkowska (2004) explored the role of diminished thyroid hormone in the distortion of cerebellar development. An attempt to understand the molecular mechanisms involved in regulation of the development of the cerebellum, the study focused on glial-neuronal interactions and specific proteins involved. The study used pregnant rats treated with propylthiouracil (PTU) to reduce thyroid function, then grouped the newborn rats by those remaining untreated and those receiving treatment with T4, comparing them with normal controls with euthyroid mothers. Cerebella of the newborns were dissected to examine the levels of proteins present in this section of their brains at various stages of development (days from birth). The data were analyzed statistically for a relationship between treatment and age using analysis of variance (ANOVA) and t-tests for any significant relationships. A significant functional decrease (expressed in protein levels) was observed at day 10, and full function was restored with T4 treatment (Li et al., 2004). The viability of treatment with T4 helps to confirm the significance of these pathways etiologically.

Other studies use treatment with thyroid hormone to examine causal relationships and pathways. A study engaged in the pursuit of related molecular and neurological mechanisms was Martinez, Eller, Viana, and Gomes (2011). The study explored the role of the pathway that includes thyroid hormone inducement of epidermal growth factor (EGF) secretion from cerebellar astrocytes, and the resultant effect on neuronal migration. The astrocyte cultures (25,000 cells in 96 cultures) were treated with T3 and compared with untreated control cultures maintained under similar environmental conditions. Cerebellar cultures (96 cultures from small pieces of cerebellar tissue) were treated using EGF. Bergmann glia (BG) fibers were extracted and grown in 96 similarly developed cultures. Divided portions of each of the BG and cerebellar cultured groups were treated with signal pathway inhibitors, while others were treated with antibodies that neutralized them against EGF. Treatment of the rat brain cultures with EGF induced significant increases in neuronal migration, whereas treatment with neutralizing antibodies against EGF or inhibition of EGF using bis-tyrphostin inhibited migration. According to this study, the results indicated that thyroid hormones, by inducing EGF secretion, promoted neuronal migration via elongation of BG fibers, bypassing the Purkinje cell layer (Martinez et al., 2011).

Since iodine is a major component of thyroid hormone, it is reasonable to consider the role of iodine deficiency in thyroid dysfunction. This consideration then leads to the important relationship between thyroid dysfunction and developmental issues or the relationship between iodine deficiency and brain damage (Delange & Lecomte, 2000). Concerns may be raised about the influence of iodine supplementation on rates of hyperthyroidism or thyrotoxicosis, but Delange and Lecomte (2000) evaluated these issues and concluded that it is better to supplement. The study thoroughly reviewed and analyzed over 60 studies for the possible ramifications of supplementation, including iodine-induced hyperthyroidism (thyrotoxicosis) or autoimmune thyroiditis, and weighed them against the results of not taking this action, including developmental issues and a debate over cancer incidence with or without supplementation (Delange & Lecomte, 2000).

Iodine deficiency and its effect on psychiatric function were examined in a 2001 study. Lederbogen, Hermann, Hewer, and Henn (2001) was a study of psychiatric in-patients throughout a calendar year. The parameters studied were total T4, free thyroxine index (FTI), and thyrotrophin stimulating hormone (TSH). Participants with thyroid dysfunction indicated by at least one parameter (243 of 880) were initially included, but the population was reduced to 848 and legitimate (not by other cause, such as drug-induced) thyroid dysfunction was determined in a resultant 100 participants. As measures of T4 and/or FTI provided no essential information in 854 patients (97% of tested), they found that in most cases the determination of TSH alone was sufficient for demonstrating normal thyroid function.

This study made the statement that TSH was sufficient measure in most cases. This is quite debatable, since TSH has been shown to be inaccurate in other studies (Schwartz, Morelli, & Holtorf, 2011). The assumption is linked to the lack of usefulness of T4 and FTI, which only illustrates the invalidity of those values. FTI is a calculated value as opposed to a measured value. Also, the active thyroid hormone is T3 and this has not been measured in any form in this study. An alternative approach would be to test the free-floating forms free triiodothyronine (FT3) and free thyroxine (FT4) to indicate the actual availability of thyroid hormone, a more direct measure of thyroid function. Therefore, this study may have miscalculated the effect.

Developmental issues, such as memory and learning disorders, may extend beyond clinical hypothyroidism to subclinical hypothyroidism, measured by the same parameters but at low normal functional levels rather than clinically low levels. Ge, Peng, Hu, and Wu (2012) suggested extending treatment to subclinical hypothyroidism, largely due to deficits in learning exhibited by lab-created subclinically hypothyroid rats. The study used 36 male rats divided randomly into 3 groups of 12 each, induced through cauterization to be clinically hypothyroid or subclinically hypothyroid, compared to non-affected controls. Thyroid function levels were measured directly using TSH, FT3, and FT4, as opposed to the calculation of FTI. The study concluded that there is a need for treatment of subclinical hypothyroidism to help prevent developmental disorders (Ge et al., 2012).

Thyroid dysfunction and endocrine disruptors may affect production of the important sex hormones progesterone and estrogen. According to Koibuchi (2008), abnormal development of the cerebellum may result from inappropriate sex hormone levels due to thyroid dysfunction. Hormonal imbalances of estrogen and progesterone may be involved, since they may be affected by production of the hormones within the Purkinje cells of the cerebellum. Additionally, rapid action of these hormones may be induced by receptor activity at cell membranes, possibly modulating the activity of neurotransmitters (Koibuchi, 2008).

Development of the cerebellum may be affected by many other factors. According to Koibuchi (2008), several inherent elements may lead to aberrant cerebellar development. Mutations of receptors may occur due to the actions of prescription drugs or environmental toxins, including endocrine disruptors, as well as the actions of hypothalamic hormones thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH), which may modulate Purkinje cell function via related receptors (Koibuchi, 2008). CRH and TRH are precursors to hormones adrenocorticotropic hormone (ACTH) and TSH which are released from the anterior pituitary to stimulate thyroid and adrenal activity in a concerted effort to balance our metabolisms. This suggests that TSH and ACTH should be used to assess metabolic activity and the status of hormones pre- and post-natally.

A rather interesting and widely-debated contributor that may affect thyroid-related developmental pathways is thimerosal. A study by Sulkowski, Chen, Midha, Zavacki, and Sajdel-Sulkowska (2012) examined the effect of ethylmercury (Et-Hg) from thimerosal on the developing brain. This is particularly interesting because of the wide distribution of vaccines containing thimerosal. In the study, pregnant rats were exposed to thimerosal during pregnancy and lactation, and their offspring were examined for auditory, motor, thyroid, and cerebellar (oxidative stress) dysfunction. The study hypothesized that perinatal exposure to thimerosal impaired development of the cerebellum, and central nervous system (CNS) as a whole, via oxidation. Dysfunctions such as a delayed startle response and significant cerebellar oxidative stress were found. In male offspring, specifically spontaneously hypertensive rats, a significant reduction in type 2 deiodinase (a selenoenzyme involved in the conversion of T4 to T3) was an evident mechanism, likely related to T3 deficiency in the cerebellum (Sulkowski et al., 2012). Thus, we have further confirmation of the effects of low T3 on the cerebellum, as well as the contribution of thimerosal (in vaccines) to developmental disorders.

Despite the many affirmative study results, there has been at least one study questioning these results. Grabe et al. (2005) concluded that evidence was limited for a pathogenic role of thyroid disorders in mental disorders. The study sampled 3,790 participants from the general population, testing the hypothesis that hypo- and hyperthyroidism were associated with mental and physical complaints, testing 38 complaints in total. The study used reasonable measures of thyroid function, directly measuring FT4 and FT3, rather than using the calculated value of FTI. Particularly, the study showed no association between psychiatric diagnoses and subclinical hypothyroidism or subclinical hyperthyroidism. However, both mental and physical problems were associated with autoimmune thyroiditis (Grabe et al., 2005).

The results from Grabe et al. (2005) and Lederbogen et al. (2001) relied on diagnosis of disorders at the functional (psychiatric) level, which could certainly be interpreted as a less precise measure, as opposed to looking directly at brain cell activity, albeit typically in rat studies of brain activity rather than human studies. An additional area of needed research is highlighted as a phenotype discrepancy between mice and human beings, which may bring some question to results yielded by Ge et al. (2012), Lederbogen et al. (2001), Li et al. (2004), Martinez et al. (2011), and Sulkowski et al. (2012), experiments with lab mice (Koibuchi, 2009). It was duly noted in Sulkowski et al. (2012) that the applied dosage of 200 mcg per kg of body weight used in the study was approximately 10 times that used in human applications, making these results somewhat suspect.

Additionally, the study by Martinez et al. (2011) was interpreted to indicate that thyroid hormones, by inducing EGF secretion, promoted neuronal migration via elongation of BG fibers, bypassing the Purkinje cell layer. However, this implies that the actions of these cultures are directly indicative of development that takes place in a closed and synergistic environment that may rely on feedback mechanisms beyond the single part, single role mechanistic model portrayed by the study. Further investigation of these roles in a more naturally-occuring environment would be appropriate. Thus, there is much room for further exploration of these mechanisms, particularly for a human study, perhaps in cadavers of former psychiatric patients with developmental disorders. According to studies such as Koibuchi (2008), estrogen and/or progesterone imbalance may be involved in cerebellar dysfunction and developmental issues. Endocrine disruptors are found in particular drugs, pesticides, parabens in makeup, industrial by-products, and heat-exposed water bottles. Therefore, the role, significance, and specific pathways of endocrine disruptors in developmental disorders may be an important area of research. In other words, the specific contribution level of endocrine disruptors to the ever more prevalent presence of developmental disorders, particularly in children with mothers exposed to these disruptors while carrying these children, is at question.

Copyright April 18, 2014

References

Anderson, G. (2008). Thyroid hormone and cerebellar development. Cerebellum (London, England), 7(1), 60-74. doi:10.1007/s12311-008-0021-4

Delange, F., & Lecomte, P. (2000). Iodine supplementation: benefits outweigh risks. Drug Safety: An International Journal of Medical Toxicology and Drug Experience, 22(2), 89-95.

 

Ge, J., Peng, L., Hu, C., & Wu, T. (2012). Impaired learning and memory performance in a subclinical hypothyroidism rat model induced by hemi-thyroid electrocauterisation. Journal of Neuroendocrinology, 24(6), 953-961. doi:10.1111/j.1365-2826.2012.02297.x

 

Grabe, H., Völzke, H., Lüdemann, J., Wolff, B., Schwahn, C., John, U., & ... Freyberger, H. (2005). Mental and physical complaints in thyroid disorders in the general population. Acta Psychiatrica Scandinavica, 112(4), 286-293.

Koibuchi, N. (2008). The role of thyroid hormone on cerebellar development. Cerebellum (London, England), 7(4), 530-533. doi:10.1007/s12311-008-0069-1

 

Koibuchi, N. (2009). Animal models to study thyroid hormone action in cerebellum. Cerebellum (London, England), 8(2), 89-97. doi:10.1007/s12311-008-0089-x

 

Lederbogen, F., Hermann, D., Hewer, W., & Henn, F. (2001). Thyroid function test abnormalities in newly admitted psychiatric patients residing in an iodine-deficient area: patterns and clinical significance. Acta Psychiatrica Scandinavica, 104(4), 305-310.

Li, G., Post, J., Koibuchi, N., & Sajdel-Sulkowska, E. (2004). Impact of thyroid hormone deficiency on the developing CNS: cerebellar glial and neuronal protein expression in rat neonates exposed to antithyroid drug propylthiouracil. Cerebellum (London, England), 3(2), 100-106.

Martinez, R., Eller, C., Viana, N., & Gomes, F. (2011). Thyroid hormone induces cerebellar neuronal migration and Bergmann glia differentiation through epidermal growth factor/mitogen-activated protein kinase pathway. The European Journal of Neuroscience, 33(1), 26-35. doi:10.1111/j.1460-9568.2010.07490.x

Sulkowski, Z., Chen, T., Midha, S., Zavacki, A., & Sajdel-Sulkowska, E. (2012). Maternal thimerosal exposure results in aberrant cerebellar oxidative stress, thyroid hormone metabolism, and motor behavior in rat pups; sex- and strain-dependent effects. Cerebellum (London, England), 11(2), 575-586. doi:10.1007/s12311-011-0319-5


 

Orthomolecular Psychiatry and Schizophrenia

Orthomolecular Psychiatry and Schizophrenia by Dr. Christopher Jackson, PhD, DOM (FL)

Introduction

In developed countries, mental illness leads to the largest proportion of disabilities compared to physical ailments (World Health Organization, 2004). Additionally, the percentage currently experiencing mental illness are about 25% of all U.S. adults, and those with at least one lifetime incident are close to 50% (CDC, 2011a). These statistics are devastating to our society and economy, as well as the lives of the affected individuals and their families. It might also be pertinent to point out that, from an orthomolecular point of view, all psychiatric conditions could be considered to have underlying physiological root causes. Therefore, this entire argument might be moot with the discovery of the underlying physiological cause(s) for any particular psychological condition.

One particularly devastating and disruptive illness is schizophrenia, with a common onset about age 21 for men, 90% with full signs and symptoms by age 30. Onset is about age 27 for women with 20% showing full signs and symptoms by age 30 (CDC, 2011b). On average, 10% of individuals with schizophrenia successfully commit suicide with a rate of attempts at 30%. Schizophrenic individuals, up to 1% of the world population, also have a high unemployment rate, adding to their own economic burdens and lessening their contributions to society (CDC, 2011b). It is estimated that the disease costs the U.S. and Canadian economies 6.85 billion U.S. Dollars annually (CDC, 2011b).

Due to the large economic and societal burden, including an association between mental illness and chronic biomedical disorders, it is suggested that there is a need for improved monitoring (CDC, 2011b). Since symptomatic treatment using antipsychotic drugs can lead to many side-effects and immune-compromising effects, some life-threatening (Tseng, 2011), it could be argued that there is a great need for understanding and treatment of the underlying cause(s), as opposed to just the symptoms of the disorders (Lesser, 2012). It is the underlying root(s) that orthomolecular psychiatry, the application of the particular (or right) molecules to psychological disorders to reverse the conditions, has begun to thoroughly explore.

Since the early days of the 1950s, when the adrenochrome theory of Abram Hoffer and Humphry Osmond defined a potential biochemical origin for schizophrenia (Mills, 2010), and the 1960s and 70s, when Nobel Laureate Linus Pauling created the term orthomolecular, based on ortho (right) molecular - finding the right molecule for the job - an evolving specialty of orthomolecular psychiatry has earned increasing recognition by mainstream medicine and psychiatry. An approach based upon nutrition and precursors to brain and neurological function may truly address the underlying causes.

The conventional approach tends to focus on correction of symptoms, rather than treatment of underlying causal factors. Treatment of symptoms may lead to a patient who feels better or is adapted better to societal norms, but whose long-term success is tied to the use of toxic drugs that damage the workings of the human body. Addressing the underlying physiological basis of each disorder (the root cause) via orthomolecular medicine/psychiatry provides hope for a true cure without dependency on refined chemicals.

Hence, this study will attempt to uncover and define the potential causal factors of schizophrenia addressed by orthomolecular medicine and psychiatry, including neurotransmitter deficiencies, genomic polymorphisms, pellagra, mercury poisoning, hyperthyroidism, stress-induced metabolites, and potential nutritional or precursor treatments for the disorder.

The fundamental theory and application of orthomolecular medicine to psychiatry, particularly schizophrenia, may help to expand the influence of the natural approach. It would be most beneficial to expand upon and complement the current approaches used in psychiatry, which too often has been dominated by cook-book dissemination of potentially harmful anti-psychotics, SSRIs, and the like (Lesser, 2012). Often, the patient is given a prescription drug or drugs to address the symptoms of the closest diagnosis. The drugs, much of the time, do not address the underlying causes (or physiological basis) of the disorders (Lesser, 2012).

The detrimental effects of the drugs have included less quality of life, a broad range of side-effects of the drugs themselves, and the hard costs and opportunity costs involved. The pursuit of an approach that offers no promise of a cure or reversal of the root causes of the disorders may simply tie the patient to a life-long pursuit of a better life via a better drug.

Addressing the Root Cause

Initially, anti-psychotic drugs may have a positive effect of recovery from psychotic episodes. This is in the short-term. Although the underlying root cause is not being addressed in most cases, the situation is reasonably resolved for a period of time. However, long-term anti-psychotic drug treatment of schizophrenia results in negative effects on quality of life. Effects include difficulty performing routine tasks due to lack of energy, lack of awareness, and lack of clarity of thought, as well as apathy, lethargy, fatigue, and a general reduction in stimulation from daily experience, largely due to tranquilizing effects (Lesser, 2012) and brain shrinkage (Ho, Andreasen, Ziebell, Pierson, & Magnotta, 2011).

Negative side-effects of anti-psychotic drug therapies include the loss or reduction of normal function physically and cognitively, while the underlying causal factors could be related to body systems, therefore quite treatable, such as thyroid function elevation, nutritional deficiencies, or the existence of heavy metals in the brain (Lesser, 2012). Neutropenia leads to lowered immunity and a potential for agranulocytosis, which may subsequently lead to fatality of the patient (Cohen & Monden, 2013; Tseng, 2011). Brain shrinkage in both white and gray matter, possibly related to a reduction of blood flow into the cerebral cortex, has also been indicated (Ho et al., 2011).

The topic of healthcare costs has been prevalent in the news and media recently, with the relatively new Affordable Care Act gradually inserting itself into the United States healthcare system. The rising cost of healthcare includes the cost of physiological and psychological care, and both areas must be considered for the needs of our nation to be properly addressed. One such consideration is the annual societal cost of childhood psychological disorders, which is approximately $247 billion, and on the rise (Perou et al., 2013). Healthcare costs exceeded general inflation between 1999 and 2009, virtually wiping out income gains (Auerbach & Kellermann, 2011).

As we have discussed, the anti-psychotic drugs do not typically address the underlying causal factors involved in the pathology of schizophrenia, and they may actually exacerbate, and further complicate, the condition with long-term exposure (Ho et al., 2011). Delving into the root cause or causes of schizophrenia and related disorders, much research has developed in the last decade, research that focuses on many underlying physiological processes. Some of the primary areas of focus are Endogenous Schizogens, Inflammation, and Genetic Polymorphisms. From related studies, one may glean greater understanding of the possible underlying factors leading to development of the disorder.

The underlying causal factors involved in the genesis of the symptoms of schizophrenia are apparently multivariate, but several possible cores come to the fore. Of these, endogenous schizogens may be metabolic by-products, hormonally active compounds, substances resulting from nutritional deficiencies, heavy metals, and others (Baumeister, 2011; Lesser, 2012; Mills, 2010). The studies presented involve the protein Taraxein, the injection of which supposedly produces the symptoms of schizophrenia (Baumeister, 2011), as well as adrenochrome, a metabolite of adrenaline, related to the production of adrenaline from stress (Mills, 2010).

Endogenous Schizogens

The Taraxein study by Baumeister (2011), a literature review, failed to substantiate the presence of this protein, indicating that its presence was unlikely. However, the author allowed for the possibility of experimental error due to incomplete or inadequate criteria. Further research into metabolites from adrenaline and other catecholamines would be suggested. In his meta-analysis, Mills (2010) examined several prior studies and concluded that he could not validate the adrenochrome hypothesis.

However, related theory would indicate that stressful circumstances may be a precursor to, or underlying trigger of, the processes leading to the development of schizophrenia. Administration of niacin (a methyl acceptor) improved symptoms of a studied schizophrenic population, theoretically by preventing or reducing the production of adrenochrome (Mills, 2011). Seybolt , 2010 showed similar results with the combination of niacin and alpha lipoic acid (ALA) administration, although results reportedly diminished after the study.

Inflammation

Inflammation is an inherent process involved in the etiology of many common health conditions. It is also evident that inflammatory processes, including hyperlipidemia, either exacerbate the condition known as schizophrenia or contribute to it (Hsu et al., 2012; Mansur et al., 2012; Müller & Schwarz, 2008; Paul-Samojedny et al., 2013; Sood et al., 2011). Hsu et al. (2012) was a large-scale study showing a prevalence of hyperlipidemia in individuals with schizophrenia.

Cytokines are chemicals involved in message transmission between cells, neuro-inflammatory responses, and the activities of the immune system. Paul-Samojedny et al. (2013) correlated cytokine polymorphisms with brain cross-talk in paranoid schizophrenia in a well-controlled study of human participants (Polish). Mansur et al. (2012) conducted a literature review demonstrating the correlation between schizophrenia and pro-inflammatory cytokines, whereas Müller and Schwarz (2008) was a literature review that also tied major depression into the relationship with pro-inflammatory cytokines. Sood et al. (2011) conducted a small, but well-controlled, rat study using aluminum to create the neurodegenerative environment.

Luckily, there are many natural approaches to the treatment of inflammation, outside the realm of the standard over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) and steroids. NSAIDs can lead to gastrointestinal disorders, as well as liver and kidney damage. Steroidal treatments can cause hormonal disruption and lead to bone disorders. A prominent member of the alternative group of natural anti-inflammatories is curcumin, and related turmeric. These are shown to address inflammatory neurodegenerative processes like those involved in schizophrenia (Sood et al., 2011).

Genetic Polymorphisms

Similarly, genetic polymorphisms are indicated as possible underlying factors in the pathogenesis of schizophrenia. A subset of cytokines is interleukins (IL). As referenced above, pro-inflammatory cytokines IL-2, TNFa, and IL-6 polymorphisms were correlated with incidence of schizophrenia. IL-6 is also involved in dopamine production, as well as other adrenal hormones that may be involved in the stress response and inflammatory responses (Paul-Samojedny et al., 2013). Effects of BDNF val66met polymorphism on dopamine receptors may relate to neurodevelopmental disturbances and severity of schizophrenia (Chang et al., 2009). Chang et al. (2009) was a well-controlled study with a reasonable sample size of 251 schizophrenic patients differentiated by age of onset and family history, as well as specific symptomatology. The sample population was compared to 284 healthy individuals. One study, also well-controlled with a sample of 208 paranoid schizophrenic inpatients and 254 control participants, indicated that correlation did not exist between polymorphism and pathology, but did exist between age of onset and pathology (Suchanek et al., 2013).

Discussion

To truly treat the underlying cause(s) of schizophrenia and similar or related disorders, we need to focus on pathophysiology, not psychology alone. A viable route to the understanding and uncovering of the information needed to treat the root cause is provided through the on-going research and theory behind the practice of orthomolecular medicine and psychiatry. The field of orthomolecular medicine has evolved from its beginnings over the last sixty plus years to a very sophisticated and scientific approach to address the need for an alternative or a complement to refined chemicals that dope and damage the body of the patient who only seeks to be helped.

Orthomolecular medicine and psychiatry may be considered a form of natural medicine, since the focus is on finding the right nutritional and precursor molecules to address the underlying causal factors involved in any disorder, particularly that of schizophrenia. Research shows that integration of natural medicine into the conventional system is strongly supported by the public (Moshe, Eran Ben, Carol, & Victor, n.d). Natural (complementary and alternative) medicine is more prevalent in higher income groups, showing that a greater proportion of individuals with discretionary spending funds tend to opt for more natural approaches to their healthcare (Hae Jin et al., n.d).

Conclusions and Recommendations

The research has shown that there are many routes to treatment, but the best solutions may be found using combinations of some or all of the following. Reducing adrenochrome (using methyl acceptors) may help to improve schizophrenia (Mills, 2010). Treatment with ALA and niacin (a methyl acceptor) improves schizophrenia (Seybolt, 2010). Further research is needed into metabolites from adrenaline and other catecholamines, and their influence on schizophrenia.

Curcumin ameliorates neuro-inflammatory processes involved in schizophrenia and other disorders (Sood et al., 2011). As stated previously, Sood et al. (2011) was based on a small population of rats. More and larger studies would be appropriate, especially in humans, relating to the effects of aluminum, pro-inflammatory cytokines, and other inflammatory substances, and their reduction using curcumin or other anti-inflammatory antioxidant substances.

Boosting immunity may offset side-effects of treatment drugs, particularly neutropenia (Cohen & Monden, 2013; Tseng, 2011). Research is needed into the underlying reason for the resultant decrease in white blood cell counts, using larger sample sizes. In the meantime, it would be prudent to test WBCs of all patients on anti-psychotics for any prolonged period of time. Research into possible nutritional, herbal, homeopathic or drug offsets to the condition would be appropriate, as well.

Treatment using omega 3 fatty acids with high concentration of eicosopentaenoic acid (EPA) may reverse brain shrinkage seen with the application of anti-psychotics. In all cases, the lowest effective dosage should be applied to avoid unnecessary diminishment of brain function, while researching an underlying cause. Thyroid function should be tested thoroughly (not just TSH), and vitamin and mineral levels should be checked for any deficiencies or excesses, as well as any significant presence of heavy metals (Lesser, 2012).

Copyright December, 2013

 

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