Have you ever heard that every snowflake is unique, just like we humans are all unique individuals? (Apologies for bringing everyone’s attention to snow because it has been the main focus our lives for the past few months… on the East Coast, at least). Well, as cheesy as that saying is, there is truth in it. Every person has a unique genetic make-up, which affects everything from eye color to enzyme activity. This week I’m staying on the topic of heart disease and omega-3s as an homage to American Heart Month, and today we discuss how we measure “omega-3 status,” how our biological individuality affects this status, and how both of these affect the interpretation of research results.
Research in the field of nutritional sciences uses different methods to assess “nutritional status.” Depending on a variety factors, everything from blood levels to questionnaires can be used to try to figure out an individual’s status. But by using different methods to determine the same status, confusion is created. In the case of omega-3 fatty acids, the three main methods of determining status are blood levels, reported intake, and research group assignment, which are discussed in further detail below.
- Blood levels, like the Omega-3 Index, are objective and take into account individual variability in compliance to dietary patterns and enzymes that affect omega-3 metabolism. If you have polymorphisms in certain enzymes related to omega-3 metabolism, you may need to eat or take higher doses of omega-3s to achieve a high Omega-3 Index. Moreover, if you are not very consistent in your intake, your blood status should reflect that. In a research study, this is very important because a participant may not want to admit that they forgot to take their supplements so they might lie to the researcher… but blood can’t lie! One drawback is that to get this data “invasive” procedures, i.e. blood draw or finger prick, are needed.
- Reported intake is a subjective measure of status because the individual has to answer questions. Commonly used surveys ask questions like, “How many times per month do you eat non-fried fish?” where the person answers with multiple-choice responses such as “>5 times per week” to “<1 time per month.” Or the individual records everything they eat for 3-7 days and we put that information into a database to estimate how much omega-3 they are getting through their food. Both of these methods are limited in their use because it requires the person to remember what they ate and report it truthfully. A recent review details how this is not an idea research method… but it seems to be the best we can do at this juncture. On the plus side, it doesn’t require a blood sample!
- Group assignment in a research study is an important aspect of study design and power calculations. For example, Group A is assigned to take 1 g EPA+DHA per day, Group B – 4 g EPA+DHA per day and Group C – 1 g corn oil (placebo). While it is important to analyze results based on group randomization, there is always the issue of subject compliance. Moreover, omega-3 supplementation predicts only ~68% of the variability in the blood omega-3 levels (Research done at Penn State in collaboration with Dr. Harris! See abstract here). This means that even if participants take their recommended dose of omega-3s faithfully, blood levels may not reach target levels due to individual variability in omega-3 metabolism that we yet cannot fully explain or predict.
Dr. H. Robert Superko and colleagues recently published a review that focused on the heart research that used blood levels of omega-3s (EPA, DPA, and DHA) to predict heart disease events and mortality. The review goes through short-term (48-hour) studies to large, primary prevention (years) trials. The authors conclude that the benefits of omega-3s seem to be concentrated in those individuals with the highest blood levels, which may or may not have been attained by participants assigned the highest dose. For example, in the JELIS Study (an EPA-supplementation study conducted in Japan), they found the group with the highest plasma EPA levels had the most significant risk reduction for heart events, but ~39% of the participants in the highest dosage group (1200 mg EPA/day) failed to reach this level. Participants in research studies whose blood omega-3 levels do not reach anticipated levels, due to compliance or metabolism issues, would not be expected to experience benefits attributed to omega-3s and would therefore dilute the effect size–another potential explanation for the lack of positive results in the recent omega-3 supplement trials.
The authors conclude that the “…blood levels of omega-3 fatty acids may be better markers of [cardiovascular disease] risk/benefit than simple assignment to a fixed dose of omega-3 supplementation.” Knowing your own individual Omega-3 Index can help you make informed decisions about how you specifically need to eat or supplement to better your health. The American Heart Association recommends two, “oily” fish meals per week as general advice for public health. Depending on your biology, you unique snowflake, you may need more, and the only way to know is to get tested.