Heavy Metals in Chocolate

 Chocolate is one of my favourite foods, and may even have health benefits.  But of course, we have to be wary of bias about health claims that we would really, really love to be true!  

 A few studies suggest possible positive mood effects from chocolate consumption, but this research looks a little bit preliminary or questionable (Shin et al).   

Other studies suggest that dark chocolate could help reduce blood pressure (see Amoah et al for a meta-analysis).  

But a recent simple RCT showed that 8 weeks of dark chocolate intake (100 mg per day) did not affect cognition (Suominen et al). 

In any case, I think chocolate, like other delicious foods, has a role in a healthy, happy lifestyle, provided of course that we stick to moderation, and that we choose products which are high quality and lower in sugar.  

The big issue in the past few weeks has been concern that chocolate contains high levels of lead and cadmium.  This was alarming to read about.  The December 2022 Consumer Reports article on this showed that many brands of dark chocolate (including my own personal favourite) contain up to  7 micrograms of cadmium and 1 microgram of lead in a typical 1-ounce serving.    They compare these numbers to California's maximum allowable dose levels, which are 4 micrograms of cadmium per day, and 0.5 micrograms of lead.    

But whenever we see a report like this, it would be important always to find out what the baseline levels are in the population, otherwise we may be much more alarmed than we need to be.  Various studies have looked at average lead and cadmium intake in the diet.   In summary, average cadmium intake in the diet ranges from 5 micrograms per day in the U.S.,  to 10-15 micrograms per day in Europe, to 30 micrograms per day in Asia, from sources such as grains, nuts, vegetables, and shellfish.  Average lead intake ranges from 2-5 micrograms per day in the U.S., to 10-30 micrograms per day in Europe and other parts of the world, from sources such as cereals, meat, and fish.  Recommendations from various sources, such as the FDA, conclude a conservative safe limit of about 58 micrograms a day for cadmium and 12.5 micrograms a day for lead, for a typical 70 kg adult, which are numbers much lower than previous recommendations. 

So the 7 micrograms of cadmium and 1 microgram of lead in a serving of chocolate is still way below most recommended safe limits, and in a ballpark comparable to existing average dietary intakes across the world.  

Of course, any amount of lead and cadmium should be reduced or eliminated in the diet.  And I hope that chocolate makers will take steps to bring down these levels.  But in the meantime, moderate daily chocolate intake is very unlikely to push your lead or cadmium levels up very much higher than they would have been otherwise; the enjoyment and possible health benefits very likely exceed the small risks.  

It will continue to be a longer-term global issue to minimize heavy metal contamination and other contaminants in food and water.  While some of this contamination is "natural," other examples are made worse by industrial pollution.  In any case, there is more work to be done to improve food safety in the coming decades.  

References:

Suominen, M. H., Laaksonen, M. M. L., Salmenius-Suominen, H., Kautiainen, H., Hongisto, S.-M., Tuukkanen, K., Jyväkorpi, S. K., & Pitkälä, K. H. (2020). The short-term effect of dark chocolate flavanols on cognition in older adults: A randomized controlled trial (FlaSeCo). Experimental Gerontology, 136, 110933. https://doi.org/10.1016/j.exger.2020.110933

Amoah, I., Lim, J. J., Osei, E. O., Arthur, M., Tawiah, P., Oduro, I. N., Aduama-Larbi, M. S., Lowor, S. T., & Rush, E. (2022). Effect of Cocoa Beverage and Dark Chocolate Consumption on Blood Pressure in Those with Normal and Elevated Blood Pressure: A Systematic Review and Meta-Analysis. Foods, 11(13), Article 13. https://doi.org/10.3390/foods11131962

Shin, J.-H., Kim, C.-S., Cha, L., Kim, S., Lee, S., Chae, S., Chun, W. Y., & Shin, D.-M. (2022). Consumption of 85% cocoa dark chocolate improves mood in association with gut microbial changes in healthy adults: A randomized controlled trial. The Journal of Nutritional Biochemistry, 99, 108854. https://doi.org/10.1016/j.jnutbio.2021.108854

Lead and Cadmium Could Be in Your Dark Chocolate. (2022, December 15). Consumer Reports. https://www.consumerreports.org/health/food-safety/lead-and-cadmium-in-dark-chocolate-a8480295550/

Cadmium and Lead Exposure. (n.d.). Retrieved January 29, 2023, from https://encyclopedia.pub/entry/2829

Koch, W., Czop, M., Iłowiecka, K., Nawrocka, A., & Wiącek, D. (2022). Dietary Intake of Toxic Heavy Metals with Major Groups of Food Products—Results of Analytical Determinations. Nutrients, 14(8), 1626. https://doi.org/10.3390/nu14081626

Supplements for Mental Health, Part 3: Omega-3 Fatty Acids & Vitamin D

Omega-3 supplements and Vitamin D have seemed very promising for years, to help with general health, depressive symptoms, cognition, or bipolar symptoms.  

But there was a very large randomized controlled trial, of over 18 000 people,  with an incredible treatment duration of 5 years.  Amazing study!  Recipients received a typical good dose of omega-3 (about 1 gram total of EPA+DHA), plus 2000 IU daily of vitamin D.   

The study showed no effect of the supplement compared to placebo.  There were no significant differences in depression rating scales, suicides, overall death rate, cancer rates, or heart disease rates.  Other findings from this study suggested some possible benefits from Omega-3 for cardiovascular health particularly for people with low dietary fish intake.  

A limitation would be that the study population comprised healthy adults.  It may be that using omega-3 supplementation in the treatment of people with established illnesses such as major depressive disorder or bipolar disorder would be more useful.  

One recent study suggested that omega-3 supplementation may have small but significant benefit in postpartum depression.  Another recent small meta-analysis suggested some benefit in treating residual depressive symptoms in bipolar disorder.   Yet, another good year-long RCT in bipolar patients showed no benefit.  

In ADHD, recent research also showed no benefit from omega-3 in a year-long study.  

In terms of other general health issues, though, there may be benefits from omega-3 and vitamin D supplementation.   The same large RCT mentioned initially (the VITAL study) showed about a 15-20% reduction in autoimmune diseases in the omega-3 or vitamin-D supplemented groups.  There is other evidence that omega-3 supplements could help in other diseases such as macular degeneration.  

So, in conclusion, omega-3 and vitamin D appear to be quite underwhelming in terms of potential mental health benefits.   But there may be some small general health benefits, for particular categories of disease such as autoimmune conditions, for people who may be at risk for deficiencies, such as those of us without much sun exposure, or for those of us who don't eat very much fish.  

Addendum: another study, published by Lavigne & Gibbons in February 2023, showed strong associations between vitamin D supplementation and a lower risk of suicide, in male U.S. veterans, with a stronger association among those with lower vitamin D levels to begin with.  But this is a retrospective cohort study, always much weaker than an RCT, and subject to potential non-causal associations.   Once again, supplementation with a standard daily dose of vitamin D is reasonable and safe; there is negligible risk of harm, with some suggestive data implying potential benefit in autoimmune conditions and mood symptoms, particularly in those who might have been deficient.   

References:

Okereke, O. I., Vyas, C. M., Mischoulon, D., Chang, G., Cook, N. R., Weinberg, A., Bubes, V., Copeland, T., Friedenberg, G., Lee, I.-M., Buring, J. E., Reynolds, C. F., III, & Manson, J. E. (2021). Effect of Long-term Supplementation With Marine Omega-3 Fatty Acids vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial. JAMA, 326(23), 2385–2394. https://doi.org/10.1001/jama.2021.21187

Mocking, R. J. T., Steijn, K., Roos, C., Assies, J., Bergink, V., Ruhé, H. G., & Schene, A. H. (2020). Omega-3 Fatty Acid Supplementation for Perinatal Depression: A Meta-Analysis. The Journal of Clinical Psychiatry, 81(5), 13281. https://doi.org/10.4088/JCP.19r13106

Kishi, T., Sakuma, K., Okuya, M., Ikeda, M., & Iwata, N. (2021). Omega-3 fatty acids for treating residual depressive symptoms in adult patients with bipolar disorder: A systematic review and meta-analysis of double-blind randomized, placebo-controlled trials. Bipolar Disorders, 23(7), 730–731. https://doi.org/10.1111/bdi.13115

McPhilemy, G., Byrne, F., Waldron, M., Hibbeln, J. R., Davis, J., McDonald, C., & Hallahan, B. (2021). A 52-week prophylactic randomised control trial of omega-3 polyunsaturated fatty acids in bipolar disorder. Bipolar Disorders, 23(7), 697–706. https://doi.org/10.1111/bdi.13037

Abdullah, M., Jowett, B., Whittaker, P. J., & Patterson, L. (2019). The effectiveness of omega-3 supplementation in reducing ADHD associated symptoms in children as measured by the Conners’ rating scales: A systematic review of randomized controlled trials. Journal of Psychiatric Research, 110, 64–73. https://doi.org/10.1016/j.jpsychires.2018.12.002

Prokopiou, K., Kolovos, P., Tsangari, H., Bandello, F., Rossetti, L. M., Mastropasqua, L., Mohand-Said, S., & Georgiou, T. (2022). A prospective, multicentre, randomised, double-blind study designed to assess the potential effects of omega-3 fatty acids supplementation in dry age-related macular degeneration or Stargardt disease. Investigative Ophthalmology & Visual Science, 63(7), 377-F0208.

Lavigne, J. E., & Gibbons, J. B. (2023). The association between vitamin D serum levels, supplementation, and suicide attempts and intentional self-harm. PLOS ONE, 18(2), e0279166. https://doi.org/10.1371/journal.pone.0279166

Supplements for Mental Health, Part 2: Zinc

 Zinc is a metallic element, and an essential nutrient.  

It is toxic if ingested in excess, with various side effects such as nausea, headache, and diarrhea.  High-dose supplementation can cause copper deficiency, typically at doses greater than 100 mg/day.  The maximum recommended dose is 40 mg/day, with the standard daily requirement being around 10 mg/day.  

The prevalence of zinc deficiency in North America is about 7.5 %  In cases of deficiency, it is obviously beneficial to use supplements.  But what about supplementation above a baseline, normal dietary intake? 

There are some positive studies, including RCTs, typically using doses of about 25 mg per day.  But a few groups have shown negative results, including a major study of using several nutritional supplements, including zinc, all at once. (Sarris et al, 2019).  This group showed that placebo did considerably better than supplements, for treating depression.   

There is in particular no evidence of benefit from zinc supplementation in the treatment of COVID.  

Overall, the research is variable, often low-quality.  It is clear, once again, that zinc supplementation is very helpful in situations in which there could be nutritional deficiencies.  

But the risk of supplementing with zinc in a 25 mg per day range would be very low.  It could be on a list of things to try, as an adjunct for the treatment of depression or ADHD.  It would best be done on a randomized basis, for example to set up your own personal study to take either zinc or placebo for 6 weeks (with the truth of what you were actually taking unknown to you until the trial was over) then with repeated randomized 6-week trials several times, to assess any consistent change in symptoms between placebo and zinc trials.  

References

Lai, J., Moxey, A., Nowak, G., Vashum, K., Bailey, K., & McEvoy, M. (2012). The efficacy of zinc supplementation in depression: Systematic review of randomised controlled trials. Journal of Affective Disorders, 136(1), e31–e39. https://doi.org/10.1016/j.jad.2011.06.022

Duncan, A., Yacoubian, C., Watson, N., & Morrison, I. (2015). The risk of copper deficiency in patients prescribed zinc supplements. Journal of Clinical Pathology, 68(9), 723–725. https://doi.org/10.1136/jclinpath-2014-202837

Estimating the Global Prevalence of Zinc Deficiency: Results Based on Zinc Availability in National Food Supplies and the Prevalence of Stunting. (2012). PLOS ONE, 7(11), e50568. https://doi.org/10.1371/journal.pone.0050568

Yosaee, S., Clark, C. C. T., Keshtkaran, Z., Ashourpour, M., Keshani, P., & Soltani, S. (2022). Zinc in depression: From development to treatment: A comparative/ dose response meta-analysis of observational studies and randomized controlled trials. General Hospital Psychiatry, 74, 110–117. https://doi.org/10.1016/j.genhosppsych.2020.08.001

Sarris, J., Byrne, G. J., Stough, C., Bousman, C., Mischoulon, D., Murphy, J., Macdonald, P., Adams, L., Nazareth, S., Oliver, G., Cribb, L., Savage, K., Menon, R., Chamoli, S., Berk, M., & Ng, C. H. (2019). Nutraceuticals for major depressive disorder- more is not merrier: An 8-week double-blind, randomised, controlled trial. Journal of Affective Disorders, 245, 1007–1015. https://doi.org/10.1016/j.jad.2018.11.092

Thomas, S., Patel, D., Bittel, B., Wolski, K., Wang, Q., Kumar, A., Il’Giovine, Z. J., Mehra, R., McWilliams, C., Nissen, S. E., & Desai, M. Y. (2021). Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial. JAMA Network Open, 4(2), e210369. https://doi.org/10.1001/jamanetworkopen.2021.036

Supplements for Mental Health, Part 1: Folic Acid

The nutritional supplement industry has a global market size of over 300 billion US Dollars annually.   This is comparable to all the money spent in the world on fresh fruit and vegetables.  

People generally take supplements with the idea that they will improve health or vitality, or prevent disease.  

What is the current evidence that supplements could help improve mental health?  I'll start by looking at vitamin and mineral supplements.  

The vitamin with the most recent attention in the literature is folic acid.  This is a B vitamin found in leafy green vegetables, oranges, and other healthy foods.  It has been established for many years as an essential supplement for pregnant women, to help reduce the risk of birth defects.  

Supplementation of folic acid during pregnancy may modestly reduce the risk of post-partum depression, but there is a lack of rigorous randomized controlled trials (RCTs) to prove this.   

The most compelling recent study was published in JAMA Psychiatry in 2022, finding a strong association between folic acid supplementation at doses at 1 mg daily, and a substantially reduced risk of suicide.   

But a major negative study was published in 2018: this was an RCT showing no reduction in depression risk with high-dose folic acid supplementation over an amazing 7 years of follow-up.  But this study did not specifically look at using folic acid as an augmentation in the treatment of people who already have depression or other mental health problems.  

A 2015 meta-analysis found no significant benefit for short-term use of folic acid as an augmentation for treating depression.  

So in conclusion, there is some evidence of folic acid being useful in treating depression or reducing suicidal ideation, but the findings are by no means definitive, and there are negative studies in RCTs.  As with many of these issues, there should be better RCTs with standardized doses (probably 1 or 2 mg daily) and longer durations, looking at using folic acid as an augmentation in people with established mental health symptoms.  In the meantime, there is negligible risk to supplementing with folic acid 1 mg daily, so it is ok to do so.  

References:

Nutritional Supplements Market Size Report, 2030. (n.d.). Retrieved 28 December 2022, from https://www.grandviewresearch.com/industry-analysis/nutritional-supplements-market

Global Marketing Associates (2021, March 8). Global fruit and vegetable market: Export opportunity analysis. Global Marketing Associates. http://www.globalmarketing1.com/food-beverage/global-fruit-and-vegetable-market-export-opportunity-analysis/

Jin, X., Cheng, Z., Yu, X., Tao, Q., Huang, R., & Wang, S. (2022). Continuous supplementation of folic acid in pregnancy and the risk of perinatal depression–A meta-analysis. Journal of Affective Disorders, 302, 258–272. https://doi.org/10.1016/j.jad.2022.01.080

Gibbons, R. D., Hur, K., Lavigne, J. E., & Mann, J. J. (2022). Association Between Folic Acid Prescription Fills and Suicide Attempts and Intentional Self-harm Among Privately Insured US Adults. JAMA Psychiatry, 79(11), 1118–1123. https://doi.org/10.1001/jamapsychiatry.2022.2990

Okereke, O. I., Cook, N. R., Albert, C. M., Denburgh, M. V., Buring, J. E., & Manson, J. E. (2015). Effect of long-term supplementation with folic acid and B vitamins on risk of depression in older women. The British Journal of Psychiatry, 206(4), 324–331. https://doi.org/10.1192/bjp.bp.114.148361

Almeida, O. P., Ford, A. H., & Flicker, L. (2015). Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression. International Psychogeriatrics, 27(5), 727–737. https://doi.org/10.1017/S1041610215000046

Mediterranean Diet for Treating Depression

Jacka et al. have just published in BMC Medicine (January 30, 2017) the results of a study showing that healthy dietary change leads to significant improvement in depression.

In their "SMILES" study (another astonishing acronym--it stands for "Supporting the Modification of Lifestyle in Lowered Emotional States" !!), they included 67 people with moderate to severe depression, who also had low dietary quality (e.g. they were not eating a lot of vegetables, fiber, fish, and nuts, but were eating a lot of processed foods and sweets).  The participants were randomized to receive 7 sessions of either nutritional counseling, or social support.  The nutritional counseling aimed to encourage a Mediterranean-style diet, including whole grains, nuts, fish, legumes, vegetables, and fruit, while avoiding sweets and processed foods.  The social support involved having neutral conversations or playing games ("befriending").

People in the nutritional counseling group dropped their depression rating scores by about 40%, while scores in the social support group dropped by only 20%, which was statistically different with a p-value of about .03.  That is, the difference in outcome was about 97% likely to be due to the treatment effect, rather than to chance.

Reflection and Conclusion

It goes without saying, in my opinion, that healthy diet must be emphasized for everyone, in order to improve all aspects of physical and mental well-being.  In depressive states, nutrition tends to be less healthy, for a variety of reasons:  people may have less energy to attend to good nutrition; their depression may cause reduced or increased appetite; there may be comorbid eating disorders; there may be medication-induced side effects affecting nutritional behaviour or metabolism; and the depression could be associated with negative economic and social factors, which are in turn related to poor nutrition.

In addition to this, it is possible that there is a direct biological effect of poor nutritional quality causing depression.

So, in order to manage depression, and all other illnesses, it is of course important to encourage healthy dietary change.

But in the case of this study, there are a few ways in which the results may seem to exaggerate the effect of the nutritional change:

First, it seems to me that any substantial positive lifestyle change could have an "active placebo" effect independent of its direct effect on mood.  Changing your diet in the ways suggested is, in my opinion, intrinsically healthy.  But in order for someone to actually make these changes, they would have to frequently make different decisions than usual in the course of their day (for example, they would eat broccoli and fish instead of a fast food burger).  It is clearly healthier to have that broccoli and fish, but the therapeutic impact of this decision may not be exclusively because of the better nutrition--it is also because the person is taking an active, disciplined step to choose something deliberately, in the name of changing their life for the better.  It is this positive intention which may be a significant part of the therapeutic impact.

People in the control group, who had conversations and card games during the 7 sessions, probably did not experience much of a sense of their lifestyle substantially changing.  I think a more interesting activity for the control group would involve something similarly "lifestyle changing" but not following the same nutritional guidelines.  

So I wholeheartedly affirm the practice of making positive dietary changes!  I have seen numerous patients who are feeling better as a result of making similar changes themselves.  But it is also important to question the conclusion of studies like this one...Here's a reason why:  suppose that there was another study which showed that buying an expensive nutritional supplement led to similar improvements in depression scores.  The supplement, in reality, could be inert, or could simply be flavoured water.  But taking the supplement would require a very active commitment on the part of participants, to alter their dietary behaviour in a consistent, disciplined way, with enthusiastic support from people claiming to be experts, over 12 weeks.  In this case, we could agree easily that the therapeutic impact of the apparent nutritional change was due to a change in disciplined habits, combined with positive expectancy, rather than due to the wholesome properties of the supplement itself.  If people were to assume, erroneously, that the supplement (and not the discipline involved to take the supplement) caused the benefit, then people would be at risk of being taken advantage of financially by the supplement manufacturers.
In conclusion,  I strongly encourage that people make positive, disciplined, healthy dietary change.  It quite probably will improve all aspects of health, including mental health.  But be careful not to overvalue the results of studies such as this one, since the same reasoning that would allow you to uncritically endorse this study's conclusions could make you vulnerable to the persuasive efforts of marketers selling products which also require disciplined adherence.

Sugar and Mental Health

There are a lot of people who make dietary recommendations.  It can be hard to figure out whom to believe.

There is a huge amount of money involved in food marketing, weight loss marketing and programs, and books about nutrition.  According to ABC News, the U.S. weight-loss industry brings in about $20 billion of revenue annually.  Another source claimed a worldwide market of a staggering $500 billion or more, for industries related to weight loss.

The issue of weight loss and food policy is a sensitive one, given the high prevalence of obesity as well as eating disorders in the modern world.   These nutritional and metabolic problems are associated with strong feelings of depression and anxiety, negative thoughts and belief about self, guilt, shame, and frustration.   Of course, there are life-threatening physical consequences of obesity as well as of other eating disorders such as anorexia. 

There are now some good documentaries available describing the history and dynamics of the food industry, particularly the industries which supply sugar and corn syrup.  For example, the films "Fed Up" (2014) or  "Sugar Coated" (2015) introduce the viewer to troubling information about large corporations sweetening the world's diet, despite abundant evidence of dangers to health.  The sugar industry has been compared to the tobacco industry, in the way that health concerns have been minimized or suppressed.   A lot of commercial advertising and other marketing directly targets children from an early age; many children associate various sweet food products with play activities, friendly cartoon characters, free toys, etc.  Some fast-food manufacturers sponsor health-related events or even resources for terminally ill children; while such charitable work is admirable, recent documentaries encourage us to consider it comparable to a cigarette manufacturer or a cocaine dealer sponsoring similar charities.   If we associate these companies with such altruism, we may be more apt to feel good about consuming their products.

Ironically, sugar itself is a required component of human metabolism.  Glucose is the main fuel for the brain.

Yet, the best way for the brain to obtain this glucose is from a diet low in sugar!  Pure sugar or other simple carbohydrates in the diet cause a sudden surge in blood glucose, triggering a cascade of hormonal changes.  Aside from the insulin response, there is a surge of pleasure from consuming sugar, which triggers an addictive behavioural sequence.

A habit of consuming sweetened foods leads to a reduction in the consumption of other nutrients.  As one develops a habit of eating sweeter things, non-sweet food items are likely to taste more bland.  It is hard for many people (especially starting off in childhood) to nurture a taste for vegetables when there are candies, ice cream, cake, cookies, or chips to choose instead.

As a component of improving mental and physical health, it is worthwhile to greatly reduce the amount of added sugar in the diet.  This reduction would be satisfying, not only due to direct improvements in your health, but also because you would be shifting your financial support away from a massively wealthy and arguably corrupt food industrial complex, towards a more wholesome industry of local farmers.

Smaller intakes of sweets and simple carbs are likely to improve your appreciation of the esthetics of other food.  Cutting sweets is not some kind of spartan sacrifice!  It will lead to greater joy and hedonic pleasure in your meals!  As you reduce sugar, your "addiction" to it will subside, allowing you to savour the tastes of all other foods, without the flavours being swamped by sweetness.  If you do end up having an occasional sweet treat, you will be able to enjoy it more thoroughly, with a smaller amount of sugar needed in the recipe.

Blueberries are good for your brain

Another study published in 2012 about dietary berry intake associated with slower rates of cognitive decline:
http://www.ncbi.nlm.nih.gov/pubmed/22535616

Here's a reference to a 2010 article by Krikorian et al. published in The Journal of Agriculture and Food Chemistry:
http://www.ncbi.nlm.nih.gov/pubmed/20047325

The article describes a randomized, placebo-controlled study in which 9 elderly adults were given about 500 ml/day of blueberry juice, with another 7 given a placebo fruit juice without blueberries. The study lasted 12 weeks, at which time cognitive and mood tests were administered.

The blueberry group clearly showed better memory performance than the placebo group, and the results had a robust level of statistical significance. The blueberry group also showed some improvement in depression symptoms.

Here's a reference to another review article on this:
http://www.ncbi.nlm.nih.gov/pubmed/18211020

The authors allude to other studies showing improved cognitive performance in animals given blueberry supplementation.

In the meantime, it seems quite sound advice to include more blueberries in your diet. An excellent snack food, a much healthier alternative than junk foods such as chips or candies, etc.

Vitamin B12

A reader recently sent in a comment wondering about the possible role of vitamin B12 supplementation in psychiatry.

Here's a brief review of the literature:
http://www.ncbi.nlm.nih.gov/pubmed/21191533     --a small case report of b12-deficient individuals responding better to antidepressants after b12 supplementation.

http://www.ncbi.nlm.nih.gov/pubmed/20976769
--survivors of stroke who took folic acid 2mg/d, b6 25 mg/d, and b12 0.5 mg/d had slightly lower rates of depression; there was an impressive 7 year follow-up period


http://www.ncbi.nlm.nih.gov/pubmed/20716710
this cross-sectional study using a diet questionnaire found an association between dietary folate & b6 and lower rates of depression in a sample of over 6000 adolescents; no association was found regarding b12.  

http://www.ncbi.nlm.nih.gov/pubmed/20519557
a study from the American Journal of Clinical Nutrition, which showed a relationship between higher folate and b12 levels, and lower rates of depression, over 7 years of follow-up.

http://www.ncbi.nlm.nih.gov/pubmed/19175490 
another study finding an association between low b12 & folate levels and higher rates of depression.  Here, the b12 association was specifically for women. Looking more closely at the data, I find that the results are not overwhelmingly strong or convincing; I suspect there could be many confounding factors influencing the association.

http://www.ncbi.nlm.nih.gov/pubmed/18854539
this is an important study from JAMA showing that high dose folate, b6, and b12 supplements did not improve the course of dementia.  Furthermore, 28% of the vitamin group experienced depression, compared to  18% of the placebo group.

http://www.ncbi.nlm.nih.gov/pubmed/18557664this study from the Journal of Clinical Psychiatry showed very little protective effect of vitamin b6, b12, and folate supplementation to prevent depression in older men.  However, I see the vitamin group did slightly better than the placebo group, but not well enough to meet criteria for statistical significance.


In summary, there is a little bit of evidence of benefits from b12 in psychiatry, but the results are not overwhelmingly strong unless there is evidence of deficiency.  It is worthwhile to have B12 levels checked.  It appears not to be dangerous to take supplements; I suppose it is reasonable to aim for the higher part of the recommended serum levels, and to adjust any supplementation accordingly.  Having said that, I acknowledge the possibility that some individuals may have a more beneficial effect from b12 supplementation, perhaps there could be selected cases in which this could act synergistically or as an augmentation with other treatments for depression, or perhaps there could be cases of subtle deficiency.

B12 deficiency is not uncommon; this can occur due to malabsorption (as in pernicious anemia or bowel disease), or due to dietary deficiency (e.g. in vegans).  If the cause of low b12 is malabsorption, is may be necessary to have b12 injections.  Once again, it is important to have b12 levels checked, and make decisions about supplementation if the level is low.

Omega-3 deficiency and low dietary omega-3 to omega-6 ratio may exacerbate depression and reduce neuroplasticity

Here's an interesting update on the dietary fatty acid issue, as it pertains to mood disorders and neuroplasticity:
http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.2736.html

This article, published in Nature Neuroscience (January 30, 2011), is an example of some good research being done by a group at the University of Bordeaux in France.  They demonstrate substantial negative neurophysiological changes in mice as a result of an omega-3 deficient diet.  It is interesting to note that the brain's endocanniboid system is specifically affected by omega-3 deficiency, according to this research.

This is further evidence supporting the importance of attending to a healthy diet, in maintaining optimal mental health.  Omega-3 fatty acids are one element of a healthy diet.  While omega-6 fatty acids are also needed in the diet, these lipids behave to some degree competitively with omega-3.  Therefore,  the ratio of dietary omega-3 to omega-6 is is very important.  Western diets tend to have an unhealthy ratio of these lipids, due to excessive omega-6. 

An ongoing issue of debate has to do with whether plant sources of omega-3 (primarily ALA) are as useful as fish sources (DHA and EPA).  Existing evidence shows that DHA and EPA are more important.  ALA can be converted in the body to DHA and EPA, but the efficiency of this may vary from person to person.

Wikipedia has a nice review of this subject: http://en.wikipedia.org/wiki/Omega-3_fatty_acid
but some of the sources are less than ideal.

It is interesting to consider that the DHA/EPA issue is not a "micronutrient" issue.  They could be considered  "macronutrients."  The solid mass of the brain consists mostly of lipids (60-80 % of the non-aqueous mass); DHA and EPA  make up over 10% of this lipid mass, which is a very high concentration.


Here's a link to a paper which quantifies the  high fractions of omega-3 lipids in brain mass:
http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=921064   --this paper also showed that dietary changes substantially altered the proportion of omega-3 lipids in brain tissue

"Vitamin Water" and "Energy Drinks"

Here's another exploitative marketing scheme going on, in the middle of university campuses:

A sugary drink, consisting of water with 23 grams (about 5 teaspoons) of sugar per 500 mL, sold in large, colourful bottles of 300 - 500 mL each  -- is being aggressively marketed to young people, with many implied claims about healthfulness.  There are funny, witty, ironic statements printed on the bottles, which I think would appeal to young adults, and consolidate the notion that these are actually healthy. 

A similar drink, which also contains caffeine and a bizarre mixture of added chemicals,  is also being aggressively marketed, with free samples being given out by smiling, athletic young people in decorated sports cars.  Today I noticed the energy drink people occupying one of the university's athletic fields with three large garishly decorated vehicles, hip musical accompaniment blaring out as they handed out samples.  It was a bothersome irony that an athletic field (another health-associated prop) had to be the setting for this.   


It is not a healthy practice to consume sugary drinks.  Aside from the risk of tooth decay, and the exposure to metabolically harmful simple carbohydrates, the habit of consuming these drinks conditions people to expect sweetness while they hydrate themselves.  Ordinary, pure, free drinking water becomes bland and undesirable.  Though the direct health effects of having a glass of sweetened water are not catastrophic, there are a variety of indirect harmful effects:

-because you are quenching your thirst, and hunger, with a solution containing glucose or fructose, you will have a smaller appetite, and less money,  to obtain or consume a healthy meal.

-because of the advertising involved, you will become conditioned to believe that you are engaging in a healthy behaviour.

-you will be financially supporting one of the largest junk food manufacturers in the world; the magnitude of harm done to the world's population (directly and indirectly) by such companies would be staggering to calculate.

-by purchasing these products, you are contributing to the phenomenon of  retailers stocking their shelves with "vitamin water" instead of with healthier choices.  In one of my favourite local cafes, my favourite healthy, locally-made fruit juice is gone, replaced by rows of multi-coloured "vitamin water."  The reason was economic -- the bright colours and the sugar make for a rapidly-selling product.


The presence of vitamins, minerals, amino acids, etc. in these products is, in my opinion, irrelevant.  It is pure marketing.  If you need extra vitamins in your day, you can take a daily supplement, or have a piece of fresh fruit.   The other ingredients are largely placebo as well, just like the colouring.

The case is made by some that there is less sugar in these drinks, compared to other familiar soft drinks.  The difference is actually not very substantial, it reminds me of cigarette companies manufacturing "light" cigarettes, to try to sell people on the idea that this is "healthier."  

I consider this type of marketing to have little ethical difference from a hypothetical example of cigarette companies hiring athletic, charming young people to hand out free samples from a flashy new car.

What bothers me most about this issue is the use of healthy-sounding nutrition talk ("vitamins," etc.) to persuade people to buy an unhealthy product.

I do not support a puritanical view of food & eating though.  I think there are many sweet, wonderful, decadent foods to be savoured (in moderation of course!)   Generally, dessert vendors do not market their tastiest pastries by emphasizing their vitamin content!  In any case, such foods can be enjoyed more richly, in smaller, healthier portions, if one is less conditioned to expect sweetness frequently through the day, such as in drinking water.  


Here are a few references to some pertinent review articles:
http://www.ncbi.nlm.nih.gov/pubmed/20631477
http://www.ncbi.nlm.nih.gov/pubmed/20682226
http://www.ncbi.nlm.nih.gov/pubmed/18809264

One exception, in which a case could be made to supplement drinks with vitamins, could be in the management of chronic, severe alcoholism.  There is a syndrome called "Wernicke-Korsakoff encephalopathy", in which severely malnourished alcoholics develop irreversible, catastrophic brain damage due to metabolism of carbohydrates without adequate vitamin B1.  Adding vitamin B1 (thiamine) to hard liquor, could conceivably prevent some cases of irreversible brain damage in malnourished alcoholics who keep drinking.  I'm not sure if thiamine would be chemically stable in an ethanol solution though--if anyone knows the answer to this one, please let me know.   Anyway, I don't believe this consideration is relevant to health management on university campuses (!)

Conclusion:  if you're thirsty, drink water!

Saturated fat not intrinsically harmful?

I'm intending to start a series of posts reviewing articles that I found interesting from a selection of journals published in the first months of 2010.


Here is the first, from The American Journal of Clinical Nutrition, March 2010, Vol. 91, No. 3, pp. 533-546.  Here's a link to the abstract:
http://www.ncbi.nlm.nih.gov/pubmed/20071648

The authors, Siri-Tarino et al., show via meta-analysis that saturated fat intake is not actually positively correlated with heart disease risk.

Rather, the more important issue is the ratio of polyunsaturated to saturated fat in the diet.  Higher ratios are protective against heart disease.

The authors cite evidence that ingesting the same number of calories as carbohydrate instead of saturated fat actually increases the risk of myocardial infarction (heart attack).

With respect to nutritional behaviour for optimal physical and mental health, I return again to the recommendation that there be a balance which includes adequate fat, carbohydrate, and protein as dietary macronutrients.  Saturated fat need not be excluded or avoided, but should be balanced by a more abundant intake of non-saturated fats.

In a separate article, the same authors recommend maintaining balanced dietary fat intake, but avoiding refined carbohydrate in the diet:
http://www.ncbi.nlm.nih.gov/pubmed/20089734

In my opinion, adequate dietary carbohydrates are very important for brain health, as I believe low-carb ketotic diets are hard on the brain.  Complex carbohydrates, with a lower glycemic index, are preferable. 

Health benefits of dietary nut intake

Dietary nut intake is strongly associated with a variety of health benefits, particularly a lower risk of developing cardiovascular disease. Here is a link to a recent review of the subject:
http://www.ncbi.nlm.nih.gov/pubmed/19321572

This 2009 article describes a carefully controlled, inpatient, 4-day randomized study in which subjects were given a breakfast containing walnuts; or a "placebo" breakfast containing the same number of calories, and the same amount of carbs & fat, but no walnuts. The results showed that a breakfast containing walnuts leads to a significantly greater feeling of satiation (contentment and satisfaction with respect to food), at lunchtime:
http://www.ncbi.nlm.nih.gov/pubmed/19910942

Therefore, eating walnuts, as part of a balanced diet, is likely to maintain a feeling of satiation, and therefore reduce some of the physiological drives which can contribute to unhealthy eating behaviours.

This is a reference to a large prospective study of over 50 000 women followed over 8 years. The results included a multivariate analysis controlling for many other factors, such as physical activity, smoking, other dietary habits, etc. There was a slight reduction in weight gain or obesity in those who included more nuts in their diet, and in fact the more frequent the nut intake, the lower the risk of obesity:
http://www.ncbi.nlm.nih.gov/pubmed/19403639

With respect to mental health, I think that a balanced, healthy diet is important. Lifestyle habits, including nutritional choices, which reduce risk of cardiovascular disease, are likely also to reduce risk of degenerative brain disease. Walnuts are a source of omega-3 fatty acids, for which there is modest evidence of beneficial effects on mood.

Treatment of eating disorders requires deliberate attention to healthy, regular nutritional habits. Many individuals with eating disorders exclude certain types of food from their diets, based on an unfounded belief that the exclusion would lead to improved control of appetite or caloric intake.

Nuts in particular clearly deserve to be part of a healthy diet, unless there are issues such as food allergy.

Chocolate & Stress

This is a sequel to one of my previous posts:
http://garthkroeker.blogspot.com/2008/10/chocolate.html

A recent study looked at various hormonal and metabolic changes associated with consuming chocolate. In this case, 30 people were given 40 g of dark chocolate daily for 2 weeks. The authors conclude that the chocolate consumption was responsible for reducing metabolic changes associated with stress, including cortisol and catecholamine excretion.

Weaknesses of the study include its brief, non-randomized, non-blinded nature (mind you, many of us would not easily be fooled by a placebo chocolate substitute!). And I see that the study is associated with the "Nestle Research Centre" in Switzerland. While I am pleased to know that a large chocolate company has a "research centre," I do have to wonder if there could be a higher risk of bias at play.

Here's a link to the abstract:
http://www.ncbi.nlm.nih.gov/pubmed/19810704

In the meantime, there is a variety of evidence out there that chocolate consumption in moderation is good for your health, in a variety of ways.

However, one concerning issue I just learned about has to do with lead contamination in cocoa and chocolate products. Lead is a heavy metal poison which should not have any presence in the diet. It can have widespread toxicity, particularly affecting the nervous system, through either acute or chronic exposure. The issue of lead in chocolate is discussed in mainstream research, such as by Rankin & Flegal (references:http://www.ncbi.nlm.nih.gov/pubmed/16757407, http://www.ncbi.nlm.nih.gov/pubmed/16203244). Based on some of this research, it may be true that raw, unprocessed cocoa nibs have no significant lead contamination, rather the lead in some cocoa and chocolate products may be the result of industrial processing.

Hopefully, manufacturers can address this issue, so that we can be reassured about safety, and so that we can get on with the enjoyment of one of life's great pleasures, knowing that it, in moderation, may also be good for psychological and medical health.

More evidence about the impact of nutrition on mood

An important paper was just published by Akbaraly et al. in The British Journal of Psychiatry, in which 3486 people were followed prospectively for 5 years, with an analysis of nutritional habits and depression symptoms. Here's a link to the abstract:
http://www.ncbi.nlm.nih.gov/pubmed/19880930


The data showed that individuals consuming a diet rich in "processed foods" (such as sweetened desserts, fried food, processed meat, refined grains, and high-fat dairy products) had a much higher rate of depression compared to those consuming a diet heavily loaded with vegetables, fruits, and fish.

The analysis controlled for confounding factors such as gender, age, caloric intake, marital status, employment grade, education, smoking, physical activity, hypertension, diabetes, and cardiovascular disease. A component of the analysis also strongly suggests that the association is not due to reverse causation, of depression leading to worse nutrition. Rather, the analysis strongly suggests that poor diet is a component of causation: that is, poor diet directly increases the risk of becoming depressed, or of having worse depressive symptoms.

Those in the third of people with diets highest in processed foods had a 58% higher chance of having clinical depression compared to the third of people with the healthiest diets.

So, once again, more evidence-based advice to eat healthily in order to protect your mental health:
-more vegetables, fruits, and fish
-less sweets, fried foods, white flour, whole milk, ice cream, etc.

Mediterranean diet is good for your brain

In this month's Archives of General Psychiatry, a study by Sanchez-Villegas et al. is published showing a strong association between lower rates of depression, and consuming a Mediterranean diet (lots of vegetables, fruits, nuts, whole grains, and fish, with low intake of meat, moderate intake of alcohol & dairy, and lots of monounsaturated fatty acids compared to saturated fatty acids). Data was gathered prospectively during a period averaging over 4 years, and was based on following about 10 000 initially healthy students in Spain who reported food intake on questionnaires.

I'll have to look closely at the full text of the article. I'm interested to consider the question of whether the results strongly suggest causation, or whether the results could be due to non-causal association. That is, perhaps people in Spain with a higher tendency to become depressed tend to choose non-Mediterranean diets. Another issue is cultural: the study was done in Spain, where a Mediterranean diet may be associated with certain--perhaps more traditional--cultural or subcultural features, and this cultural factor may then mediate the association with depressive risk.

In any case, in the meantime, given the preponderance of other data showing health benefits from a Mediterranean-style diet, I wholeheartedly (!) recommend consuming more nuts, vegetables, olive oil, fish, whole grains, and fruit; and less red meat.

ADHD questions

Here are some great questions about ADHD, submitted by a reader:

1) You write here that long-term use of stimulants has NOT been shown to improve long-term academic outcomes. Why do you think this is, given that symptoms of ADHD improve on medication? (It actually really depresses me to think that individual symptoms can improve, yet no real change takes place...though I know that this might not apply to all patients.

2) What are some effective non-drug treatments for ADHD? I am particularly interested in dietary measures, and also EEG biofeedback.

3) I have read about prescribing psychostimulants as a way of basically diagnosing ADHD...i.e., the diagnosis is based on your response to the medication. I am just wondering how precise this would be, given that stimulants would probably (?) impove most people's concentration, etc. Or is there any role for neuropsychological testing in trying to establish a diagnosis? Is there any way of definitively establishing this kind of diagnosis?

4) I have read that there are many differences between ADD and ADHD, i.e. not just in symptom presentation but in the underlying brain pathology. Is that true? I'm not sure how to phrase it, it seemed like the suggestion was that ADD was more "organic", although maybe that doesn't make sense. Does that have implications for prognosis or treatment strategies?

5) I have read that one red flag that suggests ADD in the context of MDD treatment is a good response to bupropion. If a patient did not have a really good response to bupropion-- or if the response was only partial-- does this usually mean that treatments with psychostimulants like Ritalin, Adderall, etc. will be ineffective (or only partially effective) also?

6) If ADD is not diagnosed/treated until adulthood, is it usually more difficult to treat than if it is diagnosed/ treated in early childhood? Is the response to stimulant treatment just as good? I guess I am wondering if there are certain structural changes that occur in the brain that result from untreated ADD-- kind of like long-term depression and hippocampal atrophy?

7) Is there a certain type of patient who usually does poorly on psychostimulants, or who experiences severe side effects on psychostimulants?

I don't know the answers to a lot of these, but I am interested to keep trying to learn more. Here's my best response I can come up with for now:

1) First of all, the bottom line of whether something is helpful or not may not be some specific thing, like academic performance. Perhaps "well-being" in a broad, general sense is a more reasonable goal. Yet, things like academic performance are important in life. Perhaps stimulants or other treatments for ADHD are "necessary but not sufficient" to help with ADHD-related academic problems over the longer term. It appears to me from the data that stimulants are actually helpful for academic problems, it's just that the size of the effect is much smaller than what most people would hope for.

2) I wrote a post about zinc supplementation before. Also adequate iron stores are probably important. A generally healthy diet is probably important. I've encountered some people with ADHD who have reduced tolerance for irritation or frustration, and may be particularly bothered or distracted by hunger; yet they may not be organized to have meals prepared regularly through the day. So it can help them manage their ADHD to make sure they always have snacks with them, so that they are never in a hungry state. Other than that, I think there are a lot of nutritional claims out there which have a poor evidence base. The link between sugar intake and hyperactivity is poorly substantiated--I've written a post about that.

Food additives or dyes could play a role in exacerbating ADHD symptoms. Based on this evidence, it makes sense to me to limit food dyes and sodium benzoate in the diet, since such changes do not compromise quality of life in any way, and may lead to improved symptoms. Here are a few references:

http://www.ncbi.nlm.nih.gov/pubmed/17825405
(this is the best of the references: it is from Lancet in 2007)

http://www.ncbi.nlm.nih.gov/pubmed/15613992
http://www.ncbi.nlm.nih.gov/pubmed/15155391

I once attended a presentation on EEG biofeedback. I think it is a promising modality. Harmless to give it a try, but probably expensive. It will be interesting once the technology is available to use EEG biofeedback in front of your own home computer, at low cost.

A few of the self-help books about ADHD are worth reading. There are a lot of practical suggestions about managing symptoms. Some of the books may contain a strongly biased agenda for or against things like stimulants or dietary changes, so you need to be prepared for that possibility.

3)The ADHD label is an artificial, semantic creation, a representation of symptoms or traits which exist on a continuum. Even for those who do not officially satisfy symptom checklist criteria for ADHD, they could benefit substantially from ADHD treatments if there is some component of these symptoms at play neurologically. Many people with apparent disorders of mood, personality, learning, conduct, etc. may have some component of ADHD as well: in some cases ADHD treatments are remarkably helpful for the other problems. So I think careful trials of stimulants could be helpful diagnostically for some people, provided there are no significant contraindications.

4) I've always thought about the ADHD label as just a semantic updating of the previous ADD label. Subtypes of ADHD which are predominantly inattentive rather than hyperactive may differ in terms of comorbidities and prognosis.

5) Hard to say. Many people think of bupropion as a "dopaminergic" drug, whereas bupropion and its relevant metabolites probably act mainly on the norepinephrine system in humans (its dopaminergic activity is more significant in dogs). But perhaps bupropion response could correlate with stimulant response. I haven't seen a good study to show this, nor do I have a case series myself to comment one way or the other based on personal experience.

6) I don't know about that. Comorbidities (e.g. substance use, relationship, or conduct problems) may have accumulated in adults who have not had help during childhood. Yet I have often found it to be the case that the core symptoms of most anything can improve with treatment, at any age.

7) Patients with psychotic disorders (i.e. having a history of hallucinations, delusions, or severely disorganized thinking) often seem to do poorly on stimulants. Patients who are using stimulants primarily to increase energy or motivation often are disappointed with stimulants after a few months, since tolerance develops for effects on energy. Patients with eating disorders could do poorly, since stimulant use may become yet another dysfunctional eating behaviour used to control appetite. And individuals who are trying to use stimulants as part of thrill-seeking behaviour, who are using more than prescribed doses, or who are selling their medication, are worse off for receiving stimulant prescriptions.