by Richard Aiken MD PhD @rcaiken
The US Department of Agriculture (USDA) on February 13, 2016, approved the first genetically modified (GM) apple developed to resist browning. They will go into production in the Midwest in the next few weeks (February, 2017).
Browning is caused by polyphenol oxidases (PPOs) naturally present in fruit and vegetables. When fruit is cut or bruised, these enzymes catalyze the oxidation of polyphenols to quinones, causing oxidative browning. The damage is superficial but can affect the taste and texture of the apple as well as its cosmetic qualities. In the Arctic varieties, the GM apples were genetically engineered with a transgene that produces specific RNAs to silence the expression of at least four browning PPO genes.
Is this a good idea?
The enzymes in the class polyphenol oxidase (PPO) appear to reside in the plastids of all land plants and are released when the plastid cell membrane is disrupted. PPO is thought to play an important role in the resistance of plants to microbial and viral infections and to adverse climatic conditions such as drought as although all land plants have PPO content, no PPO-like sequences have been reported in marine plants such as algae.
As stated above, in the presence of oxygen from air, the enzyme catalyzes the first steps in the biochemical conversion of phenolics to produce quinones, which undergo further polymerization to yield dark, insoluble polymers referred to as melanin. This is the same melanin that determines darkness of human skin and hair. In plants, melanin forms barriers and has antimicrobial properties that prevent the spread of infection in plant tissues.
Phenolic compounds are responsible for the color of many plants and impart taste and flavor, but more importantly, they are important phytonutrients and antioxidants.
Alteration of polyphenol oxidase
Given the activity of PPO in the adaptation of plants to, for example, plant dehydration, what are the implications of altered PPO activity on plant development, phenotype, and yield? A clear effect of PPO silencing was observed, for example, in walnut plants which developed spontaneous necrotic lesions in the leaves suggesting increased susceptibility to oxidative stress.
A potential role for PPO in photosynthesis has been speculated.
Data suggest that PPO activity can confer both a productive advantage and be associated with an increased risk of oxidative damage. While PPO activity can be associated with non-enzymatic reactive oxygen species scavenging involving flavonoid and phenolic acid substrates, a role for PPO in plant function may also be associated with its pro-antioxidant activity through the generation of secondary reaction products.
So it is obvious that the role of PPO is extensive and not fully understood. It appears premature to genetically modify plants to remove this complex molecule.
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 Araji S, Grammer TA, Gertzen R, et al. 2014. Novel roles for the polyphenol oxidase enzyme in secondary metabolism and the regulation of cell death in walnut (Juglans regia). Plant Physiology 164, 1191–1203.
 Vaughn KC, Duke SO. 1984. Function of polyphenol oxidases in higher plants. Physiologia Plantarum 60, 106–112
 Parveen I, Threadgill MD, Moorby JM, Winters A. 2010. Oxidative phenols in forage crops containing polyphenol oxidase enzymes. Journal of Agricultural and Food Chemistry 58, 1371–1382.
 Thipyapong P, Joel DM, Steffens JC. 1997. Differential expression and turnover of the tomato polyphenol oxidase gene family during vegetative and reproductive development. Plant Physiology 113, 707–718.
Adequate nutrition for younger children is a well-known critical factor for growth and development, not only in physiological terms, but also for optimal brain and cognitive function development. Inadequate nutrition has a detrimental effect on children’s health and predispose to childhood obesity, dental caries, poor academic performance, emotional and behavioral difficulties.
A cross-sectional analysis of the dietary patterns of Spanish school children ages 6 – 9 was compared with the Center for Epidemiologic Studies Depression Scale for Children Questionnaire to measure depressive symptoms. Their conclusion was that for children:
“Nutritional inadequacy plays an important role in mental health and poor nutrition may contribute to the pathogenesis of depression.”
The mechanisms behind these effects in children and adolescents are not well described.
Beyond the obvious neurologic development in utero, we know that neurologic development continues after birth and extends throughout childhood and adolescence into young adulthood. It therefore seems logical that a highly nutrient dense diet could result in an advantage in brain development with cognitive, emotional, and behavioral implications.
This could be an effect additional to the now apparent influence diet has on the mental health of adults through inflammation and the immune system, oxidative stress and neurotropic factors. Focus on psychiatric disorders in childhood and adolescence is particularly important given the fact that three quarters of lifetime psychiatric disorders will first emerge by late adolescence or early adulthood.
There is a multitude of reasons why judicious choice of dietary patterns is particularly important to establish early.
Therefore, in all practices of medicine, regardless of specialization, it is important to include nutritional habits in assessments of children, adolescents, and adults. Dietary advice and education enhances both physical and mental heath.
 Gómez-Pinilla, F. (2008). Brain foods: The effects of nutrients on brain function. Nature Reviews Neuroscience Nat Rev Neurosci, 9(7), 568-578. doi:10.1038/nrn2421.
 Rubio-López, N., Morales-Suárez-Varela, M., Pico, Y., Livianos-Aldana, L., & Llopis-González, A. (2016). Nutrient Intake and Depression Symptoms in Spanish Children: The ANIVA Study. International Journal of Environmental Research and Public Health IJERPH, 13(3), 352. doi:10.3390/ijerph13030352.
 Giedd, JN (2010) Structural MRI of pediatric brain development: what have we learned and where are we going? Neuron 67 (5), 728-34.
 Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005). Lifetime Prevalence and Age-of-Onset Distributions of DSM-IV Disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry, 62(6), 593. doi:10.1001/archpsyc.62.6.593.
Lithium was once used as a key ingredient in a soft drink invented in 1929 by Charles Leipe Grigg, an American from Price Branch, Missouri. He initially called his drink “Bib-Label Lithiated Lemon-Lime Sodas”. He later changed the name to ” 7 Up Lithiated Lemon-Lime”.
The “7” in the name comes from the atomic mass of lithium. He called his drink 7-Up presumably because of the ability of lithium to elevate the mood. These were obviously low concentrations of lithium citrate; as in deep warm springs yielding lithium salts that have been used for centuries to calm visitors at spas.
In 1962, George Winokur introduced lithium to Washington University in St. Louis (where I happened to do my adult psychiatric residency and child fellowship), having the Barnes Hospital pharmacy make up the pills and achieving an “amazing remission” in a patient who had failed on thorazine treatment and eighteen sessions of electroconvulsive therapy. This was the beginning of the widespread use of lithium in the United States for bipolar disorder and later for mania prophylaxis and still later as an adjunctive treatment for depression; it is today the only psychotropic medication that does not carry the “black box” disclaimer of potentially leading to suicidal thoughts.
The lithium ion is the third element on the periodic table and as it is just above sodium, it does have similar chemical properties to sodium. In the beginning of the twentieth century, lithium salt was prescribed as a substitute for table salt because it was not associated with high blood pressure; however, use in high arbitrary doses could lead to toxicity, so was discontinued for that purpose.
Lithium appears to be a nutritionally essential trace element found predominantly in plant-derived foods and drinking water, although its function has not been fully described. This trace element is typically present in all human organs and tissues, and is equally distributed in body water, as lithium is absorbed from the intestinal tract and excreted by the kidneys.
Recent research studies measuring the effects of trace levels of lithium, commonly found in lithia waters (on the order of 2 mg/liter compared to typical pharmacologic doses of 900 mg/ day), have demonstrated neuroprotective abilities, as well as improvements in mood and cognitive function.
Studies on the local concentration of lithium in some municipal water supplies suggest that lithium has moderating effects on suicidal and violent criminal behaviors. In addition to a whole-food varied-plant diet four 12 ounce glasses of water is recommended. I keep a paper cup dispenser near every source of water in my home and drink a five-ounce cup or two each time I wash my hands.
 Dr. Winokur, together with colleagues Eli Robbins and Samuel Guze — with whom I studied while at Washington University — established the first written formalized criteria for mental disorders, the so-called Feighner criteria, establishing the basic model for the Diagnostic and Statistical Manual series (DSM). The motivation for these criteria was totally as a way to compare research studies on similar patients and not to be taken too literally, a position lost in the many later DSM versions and now falling in disrepute. Dr. Winokur is credited with the statement “Making up new sets of diagnostic criteria in American psychiatry has become a cottage industry with little attempt at quality control”, source Glicksman, A. (2009). “Jesus Loves Me, that I Know, for the Chi-Square Tells Me So” Privileged and Non-Privileged Approaches to the Study of Religion and Aging: A Response. Journal of Religion, Spirituality & Aging, 21(4), 316-317. doi:10.1080/15528030903127155.
 Schrauzer GN (2002) Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr 21:14–21.
 Xu, J., Culman, J., Blume, A., Brecht, S., & Gohlke, P. (2003). Chronic Treatment With a Low Dose of Lithium Protects the Brain Against Ischemic Injury by Reducing Apoptotic Death. Stroke, 34(5), 1287-1292. doi:10.1161/01.str.0000066308.25088.64.
 Schrauzer, De Vroey. Effects of Nutritional Lithium Supplementation on Mood. Biological Trace Element Research Volume 40 1994 pages 89-101.
 Schrauzer, G. N., & Shrestha, K. P. (1990). Lithium in drinking water and the incidences of crimes, suicides, and arrests related to drug addictions. Biological Trace Element Research, 25(2), 105-113. doi:10.1007/bf02990271
 Armstrong, L. E., Ganio, M. S., Casa, D. J., Lee, E. C., Mcdermott, B. P., Klau, J. F., . . . Lieberman, H. R. (2011). Mild Dehydration Affects Mood in Healthy Young Women. Journal of Nutrition, 142(2), 382-388. doi:10.3945/jn.111.142000.
Iodine, an essential nutrient, is an intrinsic component of the thyroid hormone regulating metabolism at all ages and critical for fetal, infant, and child development, including neurodevelopment . Iodine deficiency is the leading cause of preventable intellectual developmental disability in the world. If iodine intake is chronically too low or too high, prevalence of hypothyroidism and hyperthyroidism may be elevated.
The daily Dietary Reference Intake (DRI) recommended by the United States Institute of Medicine is between 110 and 130 µg for infants up to 12 months, 90 µg for children up to eight years, 130 µg for children up to 13 years, 150 µg for adults, 220 µg for pregnant women and 290 µg for lactating mothers. The Tolerable Upper Intake Level for adults is 1,100 μg /day (1.1 mg/day).
Hypothyroidism results in symptoms that appear similar to clinical depression, such as low mood, low energy levels, weight gain, forgetfulness, and personality changes; it can also lead to elevated cholesterol levels.
Hyperthyroidism mimics mania and anxiety disorders, with increased activity and weight loss, difficulty sleeping, and irritability.
Reduction in the prevalence of iodine deficiency worldwide has been achieved through the fortification of sodium chloride (“table salt”; sea salt and salted processed foods are not fortified with iodine), but salting foods leads to increase in blood pressure, the major risk factor for death worldwide. Therefore, if we are not eating salted food or fish, as recommended in our whole-food varied plant diet, are we getting enough iodine?
In fact, making the dietary iodine sufficiency even more challenging, soy, flaxseeds, spinach, sweet potatoes, pears, peaches, raw cruciferous vegetables (broccoli, Brussels sprouts, cauliflower, and cabbage) and other fruits and vegetables disrupt the production of thyroid hormones by interfering with iodine uptake in the thyroid gland, acting as so-called goitrogens.
There are fruits and vegetables that may contain significant levels of iodine, but this is highly dependent on the soil from which the plant was grown. Organic farming tends to yield higher amounts of iodine because there is a greater tenancy for proper soil management and crop rotation. Some foods that may contain significant amounts of iodine include:
- Dried seaweed; a quarter ounce serving may contain as much as 4500 µg of iodine – four times the Tolerable Upper Intake Level. Unless you are a regular consumer of high purity seaweed and can adjust the amount to close to the DRI, this should probably not be your dietary source of iodine.
- Potatoes; the skin of a medium size common potato can harbor as much as 60 µg of iodine, so three potatoes could provide adequate daily intake. However, again, it depends on the soil and farming methods as well as the accompanying dietary goitrogens.
- Cranberries; can be rich in iodine with the same provisos as those listed for potatoes.
There are limited data on the dietary iodine intake of vegetarians and vegans in the United States; however, the iodine content of a Swedish vegan diet was found to be 39 µg iodine per 1000 kcal compared to a mixed diet of 156 µg per 1000 kcal. This was similar to the iodine content of German vegan diets.
The first report of iodine nutrition and thyroid function in vegans in the United States stated that Americans are at risk for low iodine intake, and these were for vegans that did allow use of iodine-enriched sodium chloride.
Therefore, for those individuals with whole-food varied-plant dietary patterns not using iodine-enriched sodium chloride, an iodine supplement is recommended. An example supplement of potassium iodide contains 225 µg.
 Delange, F. (2007). Iodine requirements during pregnancy, lactation and the neonatal period and indicators of optimal iodine nutrition. Public Health Nutrition, 10(12A). doi:10.1017/ s1368980007360941.
 Zimmermann, M. B., & Boelaert, K. (2015). Iodine deficiency and thyroid disorders. The Lancet Diabetes & Endocrinology, 3(4), 286-295. doi:10.1016/s2213-8587(14)70225-6.
 United States National Research Council (2000). Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academies Press. pp. 258–259.
 Vanderpas J (2006). “Nutritional epidemiology and thyroid hormone metabolism”. Annu. Rev. Nutr. 26: 293–322. doi:10.1146/annurev.nutr.26.010506.103810.
 AbdullaM, Andersson I, Asp NG, Berthelsen K, Birkhed D, Dencker I, Johansson CG, Ja¨ gerstad M, Kolar K, Nair BM, Nilsson-Ehle P, Norde´n A, Rassner S, Akesson B, Ockerman PA (1981) Nutrient intake and health status of vegans. Chemical analyses of diets using the duplicate portion sampling technique. Am J Clin Nutr 34:2464 – 2477.
 Waldmann A, Koschizke JW, Leitzmann C, Hahn A 2003 Dietary intakes and lifestyle factors of a vegan population in Germany: results from the German Vegan Study. Eur J Clin Nutr 57:947–955.
 As an example, Pure Encapsulations – Iodine (potassium iodide) – Hypoallergenic Supplement contains capsules of 225 µg at a daily cost of $0.12 per capsule.
At the risk of sounding reductionist, there does appear to be an insufficient intake of magnesium by most Americans. The latest data indicates that 68% of Americans do not consume the recommended daily intake of magnesium (420 mg per day) and 19% of Americans do not consume even half the government’s recommended daily intake of magnesium.
Would a serious whole-food varied-plant diet provide adequate magnesium? Maybe. But thinking of by-gone millennia in which greens were the food of choice (and spring water/ rain water the only beverage) does raise some doubts. As an example, consider spinach and oat bran, both considered good sources of magnesium.
A dose of 30 grams (one cup) of spinach minus the 27.4 grams of water content has 23.7 mg of magnesium; 96 grams of oats (one and a half cups) minus 2 grams of water has 96 mg of magnesium. But on a per calorie basis spinach has 3.4 mg magnesium compared to 0.45 mg for oats. On a per dry weight comparison spinach has 3.4 mg/g of magnesium compared to 1.7 mg/g for oats. That’s more than five times the magnesium content in spinach compared to oats.
Magnesium, one of the most essential minerals in the human body, is a co-factor in more than 600 known enzymatic reactions. Magnesium is widely connected with brain biochemistry and, as a result, a deficiency is associated with a variety of neuromuscular and psychiatric symptoms such as depression, psychosis, agitation and irritability, headaches, seizures, muscular weakness, anxiety, insomnia, fatigue, confusion and cognitive changes; this is reversible with restoration of sufficient magnesium levels.
The diets of those clinically depressed is correlated with low intake of magnesium; research indicates an inverse relationship between dietary magnesium content and depressive symptoms. Suicidal depression particularly appears to be related to magnesium insufficiency; for example, data indicate that magnesium concentration in cerebrospinal fluid was low in patients with history of suicidal behavior.
The take-home here is to eat your greens. A magnesium level may be useful as an initial clinical workup for psychiatric symptoms. If your magnesium level is verified to be low and there are accompanying psychiatric symptoms, your provider may choose to add a supplement of 600 – 800 mg per day of any of the various forms of magnesium available (except magnesium oxide, which is not bioavailable).
 King, D. E., Mainous, A. G., Geesey, M. E., & Woolson, R. F. (2005). Dietary Magnesium and C-reactive Protein Levels. Journal of the American College of Nutrition, 24(3), 166-171. doi:10.1080/ 07315724. 2005.10719461.
 Kantak, K. M. (1988). Magnesium deficiency alters aggressive behavior and catecholamine function. Behavioral Neuroscience, 102(2), 304-311. doi:10.1037//0735-7044.102.2.304.
 Papadopol V, Tuchendria E, Palamaru I: Magnesium and some psychological features in two groups of pupils (magnesium and psychic features) (2001). Magnes Res, 14, 27–32.
 Jacka, F. N., Overland, S., Stewart, R., Tell, G. S., Bjelland, I., & Mykletun, A. (2009). Association between magnesium intake and depression and anxiety in community-dwelling adults: The Hordaland Health Study. Australian and New Zealand Journal of Psychiatry, 43(1), 45-52. doi:10.1080/00048670802534408.
 Banki, C. M., Arató, M., & Kilts, C. D. (1986). Aminergic Studies and Cerebrospinal Fluid Cations in Suicide. Ann NY Acad Sci Annals of the New York Academy of Sciences, 487(1 Psychobiology), 221-230. doi:10.1111/j.1749-6632.1986.tb27901.x.
 Banki, C. M., Vojnik, M., Papp, Z., Balla, K. Z., & Arató, M. (1985). Cerebrospinal fluid magnesium and calcium related to amine metabolites, diagnosis, and suicide attempts. Biological Psychiatry, 20(2), 163-171. doi:10.1016/0006-3223(85)90076-9.