A good, balanced diet will provide the required micronutrients, experts said. Photograph used for representational purposes only

A recent article in The Lancet has estimated that the Indian population’s consumption of 15 dietary micronutrients is inadequate. Except for a small segment, most people in the world did not consume enough essential micronutrients, the article had flagged.

The article, Global estimation of dietary micronutrient inadequacies: a modelling analysis, by Simone Passarelli et al estimated that over 5 billion people worldwide, which is 68% of the global population, do not consume enough iodine; 67% do not consume enough vitamin E; and 66%, calcium. More than 4 billion people (65% of the population) do not consume enough iron; 55%, riboflavin; 54%, folate; and 53%, vitamin C.  

The study was funded by the National Institutes of Health and the Dutch Ministry of Foreign Affairs. The authors said that the analysis provided the first global estimates of inadequate micronutrient intakes, and public health practitioners could use the results to target populations requiring intervention.  

“Within the same country and age groups, estimated inadequate intakes were higher for women than men for iodine, vitamin B12, iron, and selenium; and higher for men than women for magnesium, vitamin B6, zinc, vitamin C, vitamin A, thiamin, and niacin,” the article pointed out.  

It found that that globally, more than men, women consumed lower amounts of micronutrients in the same country and age group for iodine, vitamin B12, iron, and selenium. Also, the imbalance was higher for women than men in most regions for calcium, riboflavin, vitamin E, and folate. Conversely, the prevalence of inadequate intake was consistently higher for men in the same country and age group for magnesium, vitamin B6, zinc, vitamin C, vitamin A, thiamin, and niacin. 

The researchers hoped that the analysis not only improved the understanding of global micronutrient inadequacy, but also that public health interventions can effectively address deficiencies. 

How micronutrients are consumed is important

Rema Chandramohan, Director, Institute of Child Health, Chennai, said, “This study will help us realise the importance of having a balanced diet if you are vegetarian, and eating healthy. In non-vegetarian diet, red meat rather than chicken or fish is a good source of micronutrients…”

Dr. Rema said health conditions, and the reason for malabsorption still needed to be understood. “Earlier, we used to see children with skin conditions, and other issues such as diarrhoea. Children are a lot healthier now. Accessibility to good food is better than it used to be. However, some children have inborn errors in metabolism. A majority of the time, micronutrients are absorbed from food, because we only need micronutrients in micrograms,” she added. 

Dr Rema further pointed out that issues also cropped about because of how people consumed micronutrient supplements. Iron deficiency is easily treatable with oral therapy, she said. “If you are taking iron supplement, you must consume it with juices. If taken with coffee or tea, it will retard the treatment process,” she further said. 

Meenakshi Bajaj, dietician at the Tamil Nadu Government Omandurar Multi Super Specialty Hospital, said the National Institute of Nutrition periodically releases recommended dietary guidelines for the population. “The key factors are — our requirement; the vulnerable population, whose absorption may have fallen due to certain conditions despite high intake; and the nutritional value of the food we consume,” she said.

Go traditional

Traditional food will provide the required micronutrient values, she said. It is time we avoid processed food, and return to our roots. The youth have moved away from traditional food, and the new wave of infections are not helping, she pointed out.  

“You need to go traditional. For instance, even today in villages, it is a practice to give ulundu kali (food made using black gram). It is rich in iron, vitamin B 6, and protein. There are also other sources such as sesame seed balls, which in small quantities are like small drops that add to the ocean,” she said.  

The experts further said that there was inadequate knowledge on the method of consuming a micronutrient. “For each micronutrient and enhancers, there are inhibitors. It is necessary to be armed with accurate knowledge to enjoy the benefits of natural food sources rich in micronutrients.” 

The COVID-19 pandemic has been a roller-coaster for vaccinology — from a rare show of truly global collaboration between governments, multilateral agencies, the scientific community, and industry to huge public demand for rapid vaccine development against the new virus that had brought the world to its knees to sudden concerns of “too rapid” development when many vaccines could be developed in record time. Some wanted “booster doses”, and others worried about “too many doses”.

So when the U.S. Food and Drug Administration announced in September 2021 that the third doses of the Pfizer and the Moderna COVID-19 vaccines would soon be available to Americans who were first in line to receive their initial two-shot vaccines, some experts questioned the need for it for most people — except the elderly or immunocompromised — and called it “over-vaccination” owing to a lack of data.

Later, the third dose became the norm worldwide, although India still called it a “precaution dose” and continues to do so, while many Western countries recommend repeated boosters, some with updated vaccines against the current Omicron variant. The debate over the best vaccination strategy continues.

The man who received 217 shots

In January 2022, an octogenarian from Madhepura district in Bihar claimed to have received more than 11 doses of the COVID-19 vaccine because it helped him with joint and back pain that had eluded other forms of treatment. At the time, some scientists worried about “over-vaccination”. Since the subsequent doses beyond the first two may not have been reported, it faded from the headlines.

But on March 4, a study published in The Lancet reported a shocking case of “over-vaccination” by a 62-year-old German man who received over 217 COVID-19 shots over 29 months for “private reasons”.

Researchers found out about his case from media reports and conducted a detailed study to investigate the immunological and other effects of over-vaccination on his body. Their investigation revealed much about immune function and the effects of over-vaccination. They compared their findings to a reference cohort of 29 healthy persons who received ‘only’ three COVID-19 vaccine doses.

Between November 2019 and October 2023, the researchers conducted routine examinations for various reasons, which indicated no vaccination-related anomalies on 62 parameters. No vaccine dose caused issues for the German individual. He never got a minor SARS-CoV2 infection either, according to rapid antigen/RT-PCR and nucleocapsid serology assays.

The antibody titsre were much greater than the control group vaccinees, with serum neutralisation capability 5.4-fold and 11.5-fold higher for wild-type and Omicron B.1.1.529 spike proteins, respectively.

They also reported that he exhibited antibodies that were not found in the control group and that some antibodies were also detected in his saliva. Advanced “quality” tests of antibodies showed no significant difference from the control group. Strong “over-vaccination” did not increase or impair antibody quality either.

Finally, the researchers evaluated individual immune cells to discern the “exhaustion” of immune cells from repeated vaccination — and found none. Throughout the study, more antibody titres showed the individual’s immune system’s ability to respond to the antigen despite hyper-stimulation.

In sum, even after over-vaccination, the COVID-19 vaccinations were well-tolerated and effective.

Are too many vaccine doses bad for you?

The investigations did not harm the person, and raised many questions: Are too many random vaccine doses at random intervals safe for anyone? Can a single case study generalise safety? Do two to three years suffice to assess vaccine safety? How might such high vaccine doses affect an individual’s immune system?

Many experts have discussed ‘immune tolerance’ and ‘immune exhaustion’ — especially of the T cells. Long COVID pathogenesis, when the SARS-CoV-2 virus persists in the body for a long time, has been carefully investigated in relation to this issue. Scientists have found no evidence that COVID-19 vaccinations do this. The vaccines merely briefly expose the immune system to antigens. Each shot injects a small quantity of antigen, triggering a momentary immunological response.

However, naturally sick people produce viruses and antibodies throughout the body for days or weeks. The human common-cold coronavirus and rhinoviruses infect people multiple times every year, often at short intervals, without harming their immune systems. Our immune system responds to environmental exposure on an hourly basis without getting tired. The recent vaccines are more sophisticated. They use only a portion of an organism or a few antigens, unlike smallpox and whole-cell pertussis vaccines, which include thousands.

In the new study, immunological profiling indicated repeated vaccinations or infections stimulated the immune system, making it more responsive. Interestingly, the immune system also developed faster, stronger, and broader, protecting against more new variants.

A probable downside

Cancer and HIV can cause immune-fatigue due to chronic foreign-object exposure. So the immune system might become ‘exhausted’ and stop responding after repeated encounters. Thankfully, COVID-19 has not shown this yet. Recent research has revealed that repeated vaccines and spontaneous infections in fact boost COVID-19 immunity.

Despite these promising results, over-vaccination should be avoided. The COVID-19 vaccines have been associated with autoimmune diseases like immune thrombotic thrombocytopaenia, autoimmune liver disorders, Guillain-Barré syndrome, IgA nephropathy, rheumatoid arthritis, and systemic lupus erythematosus.

Molecular mimicry, autoantibody synthesis, and vaccine adjuvants appear to contribute significantly to these disorders. The relationship between a COVID-19 shot and these conditions’ symptoms is unclear.

This said, overloading the immune system rarely causes harm. Hypervaccination may rarely cause an ‘Arthus reaction’, a condition characterised by localised acute small-vessel inflammation and possibly entire limb edema. Repeated tetanus and diphtheria vaccination injections have been shown to have this reaction.

As we know, there are two broad types of immunity: innate and adaptive. When innate immunity is permanently stimulated, and the intensity of the reactions is stronger, these mechanisms may be directed against the host and subsequently stimulate acquired immunity. The cytokines, oxidative stress, and high nitric oxide production accompany this manifestation.

Other issues pertain to the principles of immunisation. In this instance, an interval between doses ranged from two days to two months. Most vaccines, including the mRNA vaccines, work best when there is a defined minimum interval between the two doses against one particular disease. A shorter interval usually elicits a suboptimal immune response than adequately spaced doses.

One must stick to the laws of science and, in this case, the principles of vaccination. We must endorse the caution the authors advised to avoid attempting such over-vaccination without evidence on a sufficient number of subjects. In addition, the study is a good illustration of how we can seize on the opportunities to advance science for the benefit of all. Conversely, the results will also reassure the vaccine-hesitant community about the safety of vaccines.

Dr. Puneet Kumar is a clinician, Kumar Child Clinic, New Delhi, with a special interest in infectious diseases and vaccination. Dr. Vipin M. Vashishtha, is past convener, IAP Committee on Immunisation, and director and pediatrician, Mangla Hospital and Research Center, Bijnor.