Treating Hyperthyroid Cats with an Iodine Deficient Diet (Hill's y/d): Does It Really Work?

With the recent launch of the Hill’s Prescription Diet y/d Feline –Thyroid Health (1), I have been inundated with calls and emails from veterinarians and cat owners alike asking for my opinion on the diet.  According to the company marketing ads that I'm sure most if you have seen, this y/d diet is promised to "improves thyroid health in 3 weeks" and is "clinically proven to restore thyroid heath" when fed to cats with hyperthyroidism.

Since I specialize in feline hyperthyroidism, I have know about this diet some time. I've been to the Hill's Pet Nutrition Center in Topeka, Kansas, saw the cats in the feeding colony, and even had the opportunity to examine one of their many hyperthyroid cats in the colony being fed the y/d diet. During my visit, I learned a great deal about this diet, most of which has since been published as research abstracts (2,3,4) and is available online on the company's website.

Well, we all know how very inquisitive cats can be.  But it turns out that veterinarians and cat owners are inquisitive too — many have deep concerns about this diet and want to know more before they feed y/d to their hyperthyroid cats. Some of the common questions I've received include:

• How does the y/d/ diet work to lower serum T4 values? What is the mechanism of action?
• How effective is y/d in lowering T4 and controlling signs of hyperthyroidism? 
• What does y/d do to the thyroid tumor (adenoma or carcinoma) that is causing hyperthyroidism? 
• Is y/d nutritious and safe to feed hyperthyroid cats for a long time?
• Is the composition and ingredients of the y/d diet nutritious enough to feed to normal cats?

In this post, I'll start by talking about how a low iodine diet, such as y/d, can decrease serum T4 values to within the normal range in cats with hyperthyroidism. I'll also cover the effectiveness of the diet — how well does it really work?

In my next blog posts that I will write over the couple few weeks, I'll go on and try to answer some of other other questions that many of you may have concerning the composition of the diet, its effect on hyperthyroid tumor tissue, and its long-term safety concerns.

How Does Hill's y/d Diet Work To Lower Serum T4 Concentrations?

So, what's the mechanism of action of this diet? How can something as simple as just lowering the iodine level in the food "cure" hyperthyroidism? Well, iodine metabolism is actually not that simple, and as we will discuss later, it is very clear that this diet does not represent a cure — it will only work to control the disease as long as the cat only eats this diet.

As you can see below in Figure 1, iodine is one of the essential building blocks needed for thyroid hormone synthesis (5,6).  The thyroid gland actively absorbs iodide from the blood to make and release these T4 and T3 (Figure 1). The membrane "pump" that concentrates iodine within the thyroid is essential in this process and is called the sodium-iodine symporter (this Na/I symporter is also important in extrathyroidal iodine uptake, which I'll talk about in future posts). After oxidation to iodine within the thyroid follicle, T4 and T3 are made from iodination of the amino acid tyrosine, stored prior to release in an iodine-containing protein called thyroglobulin (Figure 1).

Figure 1:  Synthesis of the thyroid hormones in an individual thyroid follicular cell. 
Notice that a sodium-iodide (Na/I) symporter pumps iodide (I^-) actively into the cell. This iodide enters the follicular lumen from the cytoplasm by the transporter pendrin, in a passive manner. Once in the colloid, iodide (I^-) is oxidized to iodine (I⁰) by an enzyme called thyroid peroxidase. Iodine (I⁰) is very reactive and iodinates the thyroglobulin at tyrosyl residues in its protein chain. In conjugation (coupling reaction), adjacent tyrosyl residues are paired together. After re-entering the follicular cell, proteolysis liberates T4 and T3 into the circulation. 

Figure 2. T4 molecule
with its 4 iodine atoms

As you can see in Figures 2, T4 contains four atoms of iodine per molecule. Triiodothyronine contains one less iodine atom, thus the common abbreviation T3. Therefore, it's the number of iodine atoms in each of these thyroid hormones that determines the "number" in T4 or T3.

So, the basis for using a severely restricted iodine diet to treat hyperthyroid cats is that iodine is an essential component of both T4 and T3. With severe dietary iodine deficiency, the thyroid cannot produce adequate amounts of thyroid hormone.

Hill's y/d is clearly an iodine deficient diet, containing levels of approximately 0.2 mg/kg (0.2 ppm) on a dry matter basis, well below the minimum daily requirement for adult cats (0.46 mg/kg or 0.46 ppm) of food (1,7). It's important to note that the study that established this minimum daily requirement for cats was done by investigators funded by Hill's Pet Nutrition. So claims that this is just a low iodine diet, but not one deficient in iodine is nonsense, unless one does not believe the results of that study (7).

How Effectively Is Hill’s Prescription Diet y/d in Treating Hyperthyroidism?

According to data provided by Hill's Pet Nutrition, about 75% of hyperthyroid cat exclusively eating y/d will have normal serum total T4 concentrations by 4 weeks on the diet. By 8 weeks, 90% of cats have a serum T4 level; by 12 weeks, almost all cats should have normal values (1). This therapy appears to be more effective in cats with only moderate elevations of T4 than cats with severe hyperthyroidism.

Based on the data so far, however, the serum T4 concentrations in many cats fed this diet remain in the high-normal range, rather than the lower half of the T4 reference range. As you can see in Figure 3, the mean T4 values after feeding the diet fell to 40-45 nmol/l (3.1-3.5 μg/dl), in the upper half of the reference range limits (8).  Based on our studies, as well of the studies of other investigators (9), most older, clinically normal cats have serum T4 values  that run lower than that, typically in the lower end of the reference range (e.g., 10-30 nmol/L or 1.0-2.5 μg/dl). Therefore, in my opinion at least, that should be considered the ideal target range for success in treating cats with hyperthyroidism — no matter what therapy is used.

Figure 3: T4 values in Hyperthyroid Cats on Hill's y/d. Notice that T4 values
remain in upper half of reference range. Ideally, treated cats have T4s within
low- to mid-normal range. Graph from Hill's website (8). 

The Bottom Line

Overall, this data does indicate that feeding y/d, a diet severely restricted to overtly deficient in iodine, will result in normalization of T4 levels in most hyperthyroid cats. How well-controlled the hyperthyroid state will be maintained in cats fed y/d remains to be determined. We need additional studies to answer that question, as well as the long term safety aspect of feeding this iodine deficient diet.

Remember that all of the current data we have on this diet is based on only about 150 cats or so, most of which were colony cats at the Hill's Pet Nutrition Center.  Based on their vigorous marketing program, the Hill's pet food company is highly recommending this diet as a new treatment for hyperthyroidism, meant to replace the other time-proven therapies. They even are providing guidelines for how to weaning the cats off of methimazole and transition them on to the y/d diet.

Unfortunately for the practicing veterinarian, pet food diets are not FDA-regulated, so the company has not done the Phase II or III drug trials normally required to determine a drug's efficacy or safety. It would have nice if more research had been done to answer these questions before its release onto the market.

Based on the information we have thus far, however, this diet certainly does provide us with another option for medical management of this very common disease. But with y/d and other prescription diets, shouldn't we be also be looking at the long-term heath benefits and disadvantages for the whole cat?  Or, it is acceptable to use y/d —as some have referred to as "tunnel vision" nutrition for hyperthyroidism — and just look at its effect on serum T4 levels?

References

1. http://www.hillspet.com/products/pd-feline-yd-dry.html
2. Melendez LM, Yamka RM, Forrester SD et al. Titration of dietary iodine for reducing serum thyroxine concentrations in newly diagnosed hyperthyroid cats [abstract], J Vet Intern Med 2011;25:683.
3. Melendez LM, Yamka RM, Burris PA.Titration of dietary iodine for maintaining serum thyroxine concentrations in hyperthyroid cats [abstract], J Vet Intern Med 2011;25:683.
4. Yu S, Wedekind KJ, Burris PA, et al. Controlled level of dietary iodine normalizes serum total thyroxine in cats with naturally occurring hyperthyroidism [abstract], J Vet Intern Med 2011;25:683-684.
5. http://en.wikipedia.org/wiki/Thyroid_hormone
6. DeLange FM. Iodine deficiency. In: Braverman L, Utiger RD, eds. Werner and Ingbar's The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2000:295-316.
7. Wedekind KJ, Blumer ME, Huntington CE, et al. The feline iodine requirement is lower than the 2006 NRC recommended allowance. Journal of Animal Physiology and Animal Nutrition 2010;94:527-539.
8. http://www.hillsvet.com/pdf/ClinicalEvidenceReport-first-for-hyperthyroidism.pdf
9. Skinner ND. Thyroid hormone levels in cats: colony average and the decrease with age. Journal of Nutrition 1998;128:2636S-2638S.