Concurrent Milk Ingestion Decreases Oral Levothyroxine Absorption

At last, they have caught up with us...

Interestingly, the testing was done Following an overnight fast, and they did Total T4 testing (rather than TSH and/or Free T4).

Concurrent Milk Ingestion Decreases Oral Levothyroxine Absorption

Number: LB SUN 25

Category: Thyroid/HPT Axis

Authors

Deborah Chon MD

Body

Deborah Chon*1, Tamar Reisman2, Jane Weinreb3, Jerome M Hershman1 and Angela M. Leung4

1UCLA David Geffen School of Medicine; VA Greater Los Angeles Healthcare System, Los Angeles, CA, 2UCLA David Geffen School of Medicine; VA Greater Los Angeles Healthcare System, 3David Geffen School of Medicine at UCLA; VA Greater Los Angeles Healthcare System, Los Angeles, CA, 4UCLA David Geffen School of Medicine, Los Angeles, CA

Background: Levothyroxine is used for the physiologic replacement of thyroid hormone in patients with hypothyroidism and for serum TSH suppression in patients with thyroid cancer. In 2011, levothyroxine was the second most commonly prescribed medication in the United States, and frequent dose adjustments have been demonstrated to be a costly burden to the national healthcare system (1-2). Several studies have shown that certain foods and medications, such as calcium supplements, can interfere with levothyroxine absorption (3-5). There are no published studies specifically investigating the effect of cow’s milk, a common breakfast staple, on the absorption of levothyroxine. Cow’s milk contains approximately 450 mg of elemental calcium per 12 oz. serving.

Materials and Methods: To determine the possible effect of cow’s milk ingestion, we measured levothyroxine absorption with and without concurrent milk consumption. Pharmacokinetic studies were conducted in healthy adults without allergies to milk or levothyroxine, and who were not pregnant nor using oral contraceptives. All subjects had no history of known thyroid disease and a normal serum TSH concentration at baseline. Following an overnight fast, serum total thyroxine T4 (TT4) concentrations were measured at baseline and at 1, 2, 4, and 6 hours after ingestion of 1,000 μg of oral levothyroxine alone or when co-administered with 12 oz. of milk (2% fat). There was a four-week washout period between the two study visits.

Results: Ten subjects (mean age 33.7±10.2 years, 60% male) completed the study. The serum total T4 absorption over six hours, calculated as area under the curve (AUC), was significantly lower in those who consumed cow’s milk concurrently with levothyroxine, compared to those who took the levothyroxine alone (mean±SD: 67.26±12.13 vs.73.48±16.96; p = 0.02).

Conclusions: This is the first study to demonstrate that concurrent cow’s milk ingestion reduces oral levothyroxine absorption. The findings support previous literature showing the interference of elemental calcium with oral levothyroxine absorption. Patients managed with thyroid hormone replacement therapy should be advised to avoid taking levothyroxine simultaneously with cow’s milk.

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[ Added after some extra thought... ]

We so obviously need to know whether the impact is similar for doses more typical of people actually taking levothyroxine every day - say 100 to 200 micrograms.

We also need to know the impact of the cereal content of so many breakfast cereals (whether wheat, oats, rice, or whatever else), the fortification of breakfast cereals by iron, vitamins, etc., and the huge level of sugar often taken in or added to the cereal. This needs to be looked at along with the the milk.

It is also so very important to realise that the effect of milk might be very different in those who are hypothyroid.

Of course, trials need to be done to isolate the impacts - such as this. We also desperately need real world trials to see what effects there are.

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18 Replies

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  • Thanks for that brilliant article. I loved the part:-

    levothyroxine was the second most commonly prescribed medication in the United States, and frequent dose adjustments have been demonstrated to be a costly burden to the national healthcare system (1-2)

    Older doctors would agree except that they would have prescribed NDT and no blood test were available so it was down to their expertise and clinical symptoms.

  • Assessments of the number who need thyroid hormone medicines often count only takers of levothyroxine - that quite a number take desiccated thyroid is often ignored. Almost certainly, desiccated thyroid from Thailand and Thyro-Gold will not be counted.

  • This is a small difference and free hormone levels tend to level out more. If you are consistent in your morning milk intake (e.g. ceareals) this will make no difference as your dose is titrated to TSH, fT4 or your symptoms. Also, even if your breakfast routine varies the effects will tend to cancel out as we accumulate a little under two weeks worth of levothyroxine due to its seven day half life.

    So, in most cases this effect will have very little relevance. It will have no effect on the required frequency of blood testing contary to the authors' claim and there's no reason why patients shouldn't have milk (but not coffee) around the time of taking levothyroxine.

  • Hi, if milk and cereals can hamper the uptake of levo the doctor might not raise levo even if the tsh goes up and the patient doesn't feel so well if it is still in range. That would just be kinda tough on the patient.. Just a thought.

    Jo xx

  • That thought came to me after I wrote the post. As SlowDragon points out taking levothyroxine at bedtime is a simpler option and also allows a morning coffee if you want (need) one. It also avoids having to remember to take it when you might be in a rush and gets around all the stuff about an empty stomach and whether to take it on the day of a blood test. I always prefer the no brain option, especially when hypo has taken the brain away.

    These two studies ncbi.nlm.nih.gov/pubmed/?te... show bedtime dosing is better, although I guess some of the morning doses may have been taken with milk and possibly a few with coffee. I haven't read these papers but I think the second one is the reliable one as it was over a longer time period and placebo controlled. I would place more reliance on the comparative fT4 figures as evidence, the TSH could be affected by the fact that TSH has a circadian rhythm.

    Just take levothyroxine at bedtime, simples!

  • I'm on liothyronine and take it at bedtime, and you're right, it is simples.

    Jo xx

  • Jimh11, could you please say a bit more about what's different about having coffee?

  • ncbi.nlm.nih.gov/pubmed/183...

    Coffee has big effect on levothyroxine absorption.

  • Thanks!

  • This paper suggests that liquid and gel levothyroxine is not affected by coffee (or much less so). It is important to question whether this research is in any way managed or influenced by manufacturers...

    ncbi.nlm.nih.gov/pubmed/248...

    Some of the references to coffee fail to make it 100% clear that they are referring to unsweetened black coffee - it is obvious that milk might have an impact, so too might sugar or other sweeteners.

  • Interesting. I'd like it if there was more differentiation about some of these questions, particularly if there are some categories of food that might have a smaller impact on the effectiveness. And if T3 or NDT are impacted similarly to Levo.

    I'm currently splitting my dose into 3, so am having to eat in very small windows throughout the day :p

  • I take T3 twice a day,so if I took half at night time it would have worn off by the time I got up!

  • I take all of mine at once at bedtime. Lio.

    Jo xx

  • Hi stourie, does that work well? I take half in the morning with my Levo and half in the afternoon. I know when it is time to take the second dose as I start flagging before 3 O'clock,so it lasts about 6 hours.

  • I am on 80mcg at the moment and hope to keep it. I take it all at once at bedtime and that sees me tight through till the next dose. Hope that helps.

    Jo xx

  • Although it states take thyroxine with water and nothing else for at least half hour in the instructions. this is done for proper absorption.

  • Taking at bedtime gets round this and many find it gives better results too

    Lots of articles on net support this - e.g.

    jamanetwork.com/journals/ja...

  • I was taking my levo at bedtime but have had to change as have had such bad guts in the early morning 😢

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