VLAG blog series
From the VLAG community for the VLAG community
Blog by PhD candidate: Kesso Gabrielle van Zutphen - October 2022
A few days ago, as I was clearing up my desk, I came across a one-pager feedback that I had received from my supervisor a while ago regarding my PhD research proposal. I jokingly said to my husband I was totally going to frame it and hang it above my desk. That one-pager marked an important crossroad in my PhD journey and determined its course. As I picked up the piece of paper, I remember how this comment had struck me: “Your key research question concerns the identification of etiological factors of anemia in adolescents but, surprisingly, no data is foreseen to be collected on what is likely to be the primary cause of anemia in this risk group, namely menstruation!”
How on earth did I miss this!? Of course… menses. That one thing that just “happens” monthly and that I do not look forward to. Not sure how I managed to forget this integral part of my life as I was writing up my research proposal!
Did you know that the average woman will experience 500 menstrual cycles, spending approximately 10 years of her life menstruating? I did not. Did you know that 40% of adolescent girls suffer from dysmenorrhea and that up to one-third of women of reproductive age experience heavy menstrual bleeding? I did not. Although women have had periods since the dawn of time, the lack of knowledge on menstrual blood loss volume and the contribution of heavy menstrual bleeding to iron deficiency and anemia is striking…
Globally, iron-deficiency anemia is recognized as the number one cause of disability adjusted life years in adolescent girls aged 10 to 19. Yet, the most recent assessment of progress indicates that out of 133 countries, only two are on track to reach the global target of a 50% reduction of anemia by 2025. The message is clear: We need alternative approaches to a lingering problem. The reality, however, is that interventions to reduce menstrual blood loss are non-existent in policies, completely overlooked by the World Health Organization, and the lack of research in this area is astounding! This gap may well represent a major underestimated solution in our fight against anemia and it deserves widespread attention.
It is against this backdrop that I feel both compelled and fortunate to dedicate 4 years of my life to shed light on the contribution of heavy menstrual bleeding to iron deficiency and anemia among adolescent girls in Malawi. The ultimate goal is to improve the quality of life of thousands of adolescent girls and to safeguard their health as much as possible before their first pregnancy. Technically, I will conduct a 2x2 factorial, double-blind, randomized placebo-controlled trial. The objective is to demonstrate the effects of multiple micronutrient supplementation and/or ibuprofen during menstruation on menstrual blood and iron loss, as well as iron status.
Finally, the timing could not have been any better. It’s a very exciting time to be involved in anemia. The nutrition community is renewing efforts (at long last!) to address anemia more holistically with a more pronounced multi-sectoral lens, and my research topic is a perfect example of such an integrated approach. I’ve had countless discussions with nutritionists, gynecologists, sexual and reproductive health experts, microbiologists, infectious diseases experts, gender experts, water sanitation & hygiene, mental health experts, education experts and many more experts! All of them appreciate the multi-faceted nature of anemia and have demonstrated much enthusiasm in contributing their expertise whilst learning from us nutrition folks. More than ever, am I convinced that these exchanges and integrated systems are what will help us accelerate efforts to wipe out anemia globally.
Blog by PhD candidate: Frances Widjaja - November 2023
I want to open this blog with a proposition: “Everyone should understand the logic behind risk assessment of mixture toxicology, not just toxicologists.” Let’s see if I can convince you throughout the text.
Precisely three months ago, the people living in Dordrecht were horrified of their water. How can they not be? The same water that is used to water their vegetable gardens, and where their children swim in nature, has been contaminated with a cocktail of chemicals called per- and polyfluoroalkyl substances: PFAS has been and is now again becoming media highlight. One member of the group called PFOA is possibly carcinogenic to human, and its level was found to be way higher than what the Dutch RIVM considers as safe. Scary? I bet.
People tend to fear man-made chemicals such as PFAS, because artificial products are perceived to be less safe than what nature offers. But does natural mean safe? If all natural products are safe, I won’t be spending four years on a PhD studying plant toxins that make their way into our food chain. Although these plant toxins are less famous than PFAS, and not as easy to pronounce (I promise I will only mention it once: pyrrolizidine alkaloid N-oxides, there you go), they are also cocktail of chemicals that can cause liver tumor and cancer in the long run. As they are natural plant toxic metabolites found in 3% global flowering plants, they might contaminate crops such as wheat, barley, and even food products such as honey, tea, plant food supplements, salads, herbs and spices.
Imagine that you and I work at the regulatory agency; we are tasked to decide if the maximum level permitted of certain group of chemicals is still safe or must be changed. How do we precisely do that when there are 660 members in that group? On the one hand, adding everything up and assuming they are equally toxic is too conservative because some might be less toxic than the others. On the other hand, taking the “less-toxic” out of the equation might underestimate the real danger. That’s when they hired me to figure out this so-called relative potency for the purpose of risk assessment.
One of the goals of a toxicologist is to figure out whether a certain chemical is safe for most of the human population, and not just for 3-4 individual rats. Yet, testing chemicals directly on human is unethical, and monitoring exposure level often do not give clear link between occurrence, consumption and effects. So, we first built a computer model for rat, validated the model with rat data, built a model for human based on what we have for rat, and lastly a model for a population of human.
My initial task was to obtain a single number of relative potency, say 0.5 or 0.8, when comparing the toxicity of chemical A to chemical B. But science being science, it is full of surprises (which is one of my motivations to keep working in science even after I’m finished with this PhD!). This “single number” turns out to depend on dose, as depending on the dose level you’re looking at, the relative potency changes! My promotor and I certainly didn’t expect that. Not only dose, but the choice of endpoint also matters to the relative potency values. By the time I am writing this blog, I am still working on the extent of effect coming from individual donor – science is always in progress.
Now, coming back to my proposition, I am not saying that everyone should spend a four-years PhD assessing the risks of chemicals in a toxicology lab. It is our job as toxicologists to spread our research findings in a clear and relevant way: to make sure you understand why certain studies matter, and what we have learnt from it. But if you don’t understand how regulatory agency makes their decision (such as whether the water in Dordrecht is safe to swim in again, or whether we can drink certain tea and supplement products as often as we want), there will be no trust in the society and that doesn’t help anybody. Finally, quoting Dr. Angela Bearth from ETH Zurich: ”People should be aware of the risk. People should be knowledgeable and not be misled. People need to be motivated to protect their own health, health of others and the environment.”