Untargeted iron supplementation for anemic but not iron deficient populations

I am tuning in from winter in Cambodia (there was a cold-weather advisory recently… this afternoon it got up to 29 degrees). Thank you for your patience in the LONG silence between posts.

I am more than overdue to provide you with an overview of the nutrition research that my university is conducting in collaboration with a local NGO in Phnom Penh that I have the privilege to be a part of. AKA we are answering the “what are you researching?” question. We are about to get real science-y but I promise you I’ll really break it down. Stick with me…

Let’s start off with some background and definitions.
Anemia -What is it? Hint: it’s not “iron deficiency”. Well, at least not simply that.

Anemia is a huge problem worldwide, affecting over 1.5 billion people (yes, you read that right). Anemia is when you have low red blood cells, meaning not enough oxygen is circulating around your body reaching vital tissues, causing fatigue, decreased work productivity,  and adverse pregnancy outcomes, just to name a few of its detrimental consequences.

Oftentimes, people think iron deficiency is synonymous with anemia, but this is not true and it is important to understand the difference.

Hemoglobin is a protein in your red blood cells that binds iron, making iron an essential element for red blood cell production. Iron deficiency has 3 stages. In the most severe stage, when iron stores are exhausted, there is inadequate iron for sufficient red blood cell production. This refers to iron deficiency anemia and is generally assumed to cause about half of all anemia cases worldwide. But many other things can also cause anemia: other micronutrient deficiencies (folate, vitamin B12), excessive blood loss through heavy menstruation, inflammation, infection (eg malaria), or genetically inherited disorders affecting hemoglobin production (aka genetic hemoglobin disorders).

A diagram I made of the relationship between iron deficiency and anemia in a hypothetic population

Global recommendations state women of reproductive age should consume 60mg iron supplements daily for 3 consecutive months each year in countries where anemia prevalence is greater than 40%, including Cambodia (with 45% of women having anemia in 2014!!!).  This recommendation is based on the assumption that ~50% of anemia in low-income countries is caused by iron deficiency (ID), along with the well-established benefit of iron supplementation to correct ID. It is important to note that iron deficiency is only one (of the many) causes of anemia and giving iron to anemic women will only be helpful if iron deficiency is the cause of their anemia.

It has generally been assumed that, in Cambodia, the majority of anemia is associated with insufficient iron intake. The country has adopted many iron supplementation programs, such as iron and folic acid pills for pregnant- women, iron in birth control pills, and fortifying fish sauce country-wide with iron, but rates of anemia have not changed over the years. In recent studies, they found a low prevalence of iron deficiency – only ~3% of Cambodian women had ID. So, if iron deficiency is not the major cause of anemia in a population, untargeted iron supplementation and is a waste of resources; and at worst, it could cause harm.

Anemia in Cambodia is largely associated with genetic hemoglobin disorders (60% of women have these disorders!!), making the potential for iron supplementation to cause harm especially true, as these disorders cause altered iron metabolism and an increased risk of iron overload

Given global policies and implementation programs, it is necessary to understand the potential harms of supplementation. Countless studies have reported on the benefits of iron supplementation and fortification but there is a huge lack of research looking at harm, beyond gastrointestinal upsets (if you’ve taken iron pills before you may know you can get stomach aches or other GI symptoms). Excess iron is known to be associated with many consequences, including oxidative stress, DNA damage, gut pathogen abundance and gut inflammation. When you have excess iron siting unabsorbed in your colon it feeds pathogenic bacteria, overriding beneficial bacteria, throwing off the equilibrium of the gut microbiota, resulting in increased inflammation within your gut.

The risks are made greater because the type of iron that is commonly used in large-scale programs is poorly absorbed. Typically, less than 20% is absorbed in the gut; the remaining 80% passes unabsorbed in the colon, where it can increase that risk of pathogen growth and gut inflammation. But what if a higher bioavailable form of iron was given? This way a much lower (and potentially safer) dose would be necessary.


If you are still reading WELL DONE! I appreciate your curiosity!

So after that long background…. our study is seeking to understand the safety of blanket iron supplementation in anemic populations where iron deficiency is not the main cause of anemia and hemoglobin disorders are common.

We are comparing a newer type of iron that is much better absorbed (giving a much lower dose) to the conventional form and dose or iron recommended worldwide. This novel iron is very common in Canada, USA and Europe. We are comparing how these forms impact iron levels in the body as well as markers of potential harm in the gut, DNA and more.

We are recruiting women from a rural province 3 hours away from the capital city of Phnom Penh. Participants will be randomly assigned to one of the three treatment arms, and receive supplement bottles with instruction to take a pill every day (either (1) conventional iron, (2) high bioavailable iron or (3) placebo [control group]).

I am working with a fantastic team as we move through the many stages of the study: recruitment, enrollment, questionnaires, blood and stool collection time points and continual monitoring visits over 4-5 months.

One of our data collectors explaining the study and answering questions in order to recruitment women through signing a consent form.

The hope of this study is that it will contribute to the evidence for safe and effective iron supplementation for women in Cambodia and worldwide.

I will post day-in-the-life field updates along the way with lots of photos because I know that this will be the more exciting part to read about! Stay tuned. I pinky promise I won’t take months before my next update.

Touchdown

It has been one week since I’ve arrived in Cambodia. It is 36°C and feels like 41°C. I like to think I handle the heat really well but I feel lethargic here. It’s like someone unplugged my side and my energy is draining out. Cambodians drive by on their motos with sweaters, jeans and helmets on. How?

As many of you know I began my masters in Vancouver last fall in Human Nutrition. Many of you also know my love for adventure and the passion I have for development issues and adequate health access and food security for all. With that focus, I found myself on a project where I will conduct my research in rural Cambodia for a few months through a local NGO partnership that my university has a longstanding relationship with. In future posts, I will explain the rationale for our research and answer the classic question grad students get: “so, what exactly IS your research?” A very full explanation is to come, along with my research journey here in South East Asia, but for now, I thought I’d fill you in on the past few fun days since I’ve landed.

Upon arriving, I was immediately overwhelmed with the smells, loud honks, and sights blurring by me. As we would speed through the streets on a tuk-tuk, a sea of motos would weave through traffic. Over half a million people drive moto’s in Phnom Penh, with often more than one person on the back (2, 3, or a whole family!) Our driver was even facetiming his friends while simultaneously swerving through bumpy streets (mom, I’m fine)! Being in moto traffic can best be described as organized chaos, but its tons of fun and it defines life in Phnom Penh!

Jelisa caught me in action trying to catch some of the cool breeze! (No I am puking out the side of a tuk tuk!)
Jelisa caught me in action trying to catch some of the cool breeze! (No I am puking out the side of a tuk tuk!)

MANY of you may know of my bad jaywalking habit but it is safe to say if Phnom Penh jaywalking is level 10, I was only living level 1 difficulty in Canada. Despite the craziness of streets, if you need to cross the road you just go and vehicles will stop for you. My friend just set out across a crazy busy roundabout and told me to follow … I think a forgot to breathe for a minute. I guess I am not as traffic brave as I like to think.

This busy capital has so many beautiful temples and architecture scattered throughout the main arteries of the city or stunning monuments at the center of roundabouts. Pictured here is the Royal Palace, Tuol Tompoung Pogoda and the Independence Monument, to commemorate Cambodia’s independence from the French in 1953.

 

Independence Monument
Tuol Tompoung Pogoda
Tuol Tompoung Pogoda
Royal Palace
Wat Langka

A fun observation I’ve made about this city: they have streets with every shop dedicated to selling the exact same item. This is not an exaggeration: on my drive in from the airport my friend pointed out we were driving through the fan area where every.single.shop. had the same small and large fans set up on the sidewalk and inside their open shops. My current favourite is the durian street. For those of you who don’t know, durian, known as the “King of Fruit” is yellow with a large spiky exterior. But the defining feature of durian is its unmistakable odour, that many (including myself) liken to the smell of onion and dirty gym socks. Something I will never forget, my first time on the Singapore Subway I noticed a sign saying: “No Smoking. No flammable objects. No Durian.” Enough said. Anyway, I came across “durian street” the other night, and have recently learned that the fruit is just in season. Every shop was overflowing with people putting their large fruits on scales. Quite a sight to behold.

Moving onto everyone’s favourite part: food. We’ve eaten lots of good food (no durian, yet) here – Cambodian, Western, French, Chinese and Indian. I am on the hunt for all the good vegeterian spots and have already found a couple of gems! A traditional Cambodian dish, Amok, is a slightly sweet curry, usually with fish, steam cooked and served beautifully in a banana leaf. The street food is a staple, as it is cheap ($~1 dollars for a substantial bowl of fried rice or noodle soup) and provides the authentic experience of eating cross-legged on mats in the middle of the night market. My friend took me to her favourite place, Katy Peri Pizza, which did not disappoint! Wood-fired pizza cooked on the back of a moto and a business name like that – I am sold!

  

I attended my first Khmer language class (pronounced: Kha-my) this morning and am excited to expand my vocabulary beyond “hello” “thank you” “good morning” and “good night”. But when a language looks like this: ជំរាបសួរពីប្រទេសកម្ពុជា it may be a long road ahead.

On a more serious note, to prepare for my travels, I began learning about Cambodia’s history and how the turmoil of recent decades has devastated all aspects of Cambodian culture and development. The Khmer Rouge was a brutal regime that controlled Cambodia from 1975 to 1979, where 1.5 to 3 million people (25% of the Cambodian population) were killed. The Communist party’s goal was to create a classless state based on a rural agrarian economy, rejecting the free market and capitalism, and therefore killing off the brightest minds, such as doctors, business professionals, and others that had migrated to the city.

I visited the genocide museum, S21, a former high school used as Security Prison 21 by the regime where thousands of people (Cambodians and foreigners) were tortured and executed. I spent 2 hours wandering through the grounds, listening to an audio tour on a quiet day, experiencing most of the rooms on my own. It was raw and shocking. The audio tour held nothing back while explaining the atrocities committed by the Khmer Rouge. I was brought to tears and feel it was important to gain greater insight into the events that impact modern day Cambodia.

Lastly, something that has really bothered me here is the excessive use of single-use plastic and the absence of recycling programs. Although much progress still needs to be made with regards to sustainability policies and practices, Canada has become comfortable talking about the shocking truths of our wasteful lifestyles and big changes are happening. Here, I am saddened to see most people carry their drink in a plastic cup, with a plastic straw, all in a transparent plastic bag (so unnecessary!) to sling onto the handlebars of their moto or vegetables sold wrapped in plastic wrap and placed in styrofoam containers held in place by more cling wrap. We were wandering the streets looking for a lunch spot and came across a waste-free restaurant! All their packaging materials are biodegradable and the drinking straws are made from bamboo. We were happy to give them our business and peruse their small selection of waste-free items for eating, drinking and grocery shopping.

While half my time will be spent in the metropolitan capital, the other half will be in Kampong Thom province, where I will conduct my research. From the two days we spent there this week, the city is much more rural, lacks the flushing toilets of the big city and foreigners are a rare sight there, but it was equally refreshing to get a break from the hustle and bustle. I may have gotten enough bug bites, despite my bed mosquito net, to ensure I will never forget my bug spray in Phnom Penh ever again!

I’ve been taking the time to acquaint myself with the city, get adjusted to the time change and heat as well shadow another nutrition project happening with the same NGO run by another Canadian university until ours becomes underway. Thanks for reading all the way through this long thing and I look forward to sharing about the beginning stages of our study and life here in Cambodia! លាហើយ “Lee hi !” 

Spam prevention powered by Akismet