Wednesday, February 1, 2023

Why to get your COVID bivalent booster

The COVID vaccines have saved millions of lives, and spared millions more a frightening hospital or intensive care admission.   Many people may not realize that recovery from a COVID hospitalization will often not be complete; tissue damage from COVID pneumonia may not heal completely, also the psychological effect of respiratory failure should not be underestimated.  Severe respiratory failure (a terrifying, suffocating experience) can often be a cause of PTSD that could affect you psychologically for years afterwards.   The vaccines have caused a huge reduction in such episodes of respiratory failure.  

COVID vaccinations are not perfect, and their protective effect does diminish gradually with time, though does not disappear entirely.  There are indeed rare cases of serious adverse effects, much lower than the rate of similar or worse adverse effects from COVID itself.  Also, vaccination reduces the probability of spreading to other people, thereby multiplying the beneficial effects in the whole community.  Vaccination followed by a mild case of COVID a few months later likely adds robust protection compared to vaccination or infection alone.   But the most effective and safe protection is to have an updated bivalent COVID booster, particularly if your last dose of vaccine and any episode of COVID infection has been more than 2-3 months before present.  Unfortunately, fewer people have had their boosters compared to previous vaccine doses, resulting in thousands of needless hospitalizations and deaths.  

Anti-vaccine misinformation is widespread, with testimonial accounts from people claiming that the vaccines are harmful.  It is important to know that a bivalent booster will lead to a large reduction in risk of severe disease, hospitalization, ICU admission, and death.    Evidence to support this is very, very robust, and unfortunately has not been emphasized strongly enough in current public health information campaigns.  

I encourage perusing the references below.  Aside from reading the studies and assessing the evidence for yourself, I encourage you to look up the authors and verify for yourself that these are incredibly experienced, well-educated researchers from major research centers, with no major biases or profit motives affecting their findings.    The research findings are corroborated and consistent with the  experience of ICU and infectious disease physicians, who on a daily basis in the past months have continued to see much more severe COVID disease and dangerously high hospital occupancy among those who are not up-to-date with their booster vaccinations.  

The references below are a preliminary list; I encourage you to continue checking out other references I've included in my previous COVID-related posts.  


Watson, O. J., Barnsley, G., Toor, J., Hogan, A. B., Winskill, P., & Ghani, A. C. (2022). Global impact of the first year of COVID-19 vaccination: A mathematical modelling study. The Lancet Infectious Diseases, 22(9), 1293–1302.

CDC. COVID Data Tracker.  Centers for Disease Control and Prevention.

Arbel, R., Peretz, A., Sergienko, R., Friger, M., Beckenstein, T., Yaron, S., Hammerman, A., Bilenko, N., & Netzer, D. (2023). Effectiveness of the Bivalent mRNA Vaccine in Preventing Severe COVID-19 Outcomes: An Observational Cohort Study (SSRN Scholarly Paper No. 4314067).

Lin, D.-Y., Xu, Y., Gu, Y., Zeng, D., Wheeler, B., Young, H., Moore, Z., & Sunny, S. K. (2023). Effectiveness of Vaccination and Previous Infection Against Omicron Infection and Severe Outcomes in Children Under 12 Years of Age (p. 2023.01.18.23284739). medRxiv.

Andersson, N. W., Thiesson, E. M., Baum, U., Pihlström, N., Starrfelt, J., Faksová, K., Poukka, E., Meijerink, H., Ljung, R., & Hviid, A. (2023). Comparative effectiveness of the bivalent BA.4-5 and BA.1 mRNA-booster vaccines in the Nordic countries (p. 2023.01.19.23284764). medRxiv.

Davydow, D. S., Gifford, J. M., Desai, S. V., Needham, D. M., & Bienvenu, O. J. (2008). Posttraumatic stress disorder in general intensive care unit survivors: A systematic review. General Hospital Psychiatry, 30(5), 421–434.

Tenforde, M.W. et al. (2022). Early estimates of bivalent mRNA vaccine effectiveness in preventing COVID-19-associated emergency department or urgent care encounters and hospitalizations among immunocompetent adults. VISION Network, nine states, Sep-Nov 2022.  Morbidity and Mortality Weekly Report, 71(5152), 1616-1624. 

Sunday, January 29, 2023

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.  


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.

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.

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.

Lead and Cadmium Could Be in Your Dark Chocolate. (2022, December 15). Consumer Reports.

Cadmium and Lead Exposure. (n.d.). Retrieved January 29, 2023, from

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.

Friday, December 30, 2022

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.   


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.

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 Psychiatry81(5), 13281.

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.

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.

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.

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.

Wednesday, December 28, 2022

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.  


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.

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.

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.

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.

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.

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.

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.  


Nutritional Supplements Market Size Report, 2030. (n.d.). Retrieved 28 December 2022, from

Global Marketing Associates (2021, March 8). Global fruit and vegetable market: Export opportunity analysis. Global Marketing Associates.

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.

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.

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.

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.