FDA Addresses the Issue of Therapeutic Pet Foods

The U.S. Food and Drug Administration (FDA) is scrutinizing pet foods with labels claiming to treat or mitigate disease, suggesting that the sale of some brands call for a veterinary directive much like that of prescription medications.

Last week, the FDA released a draft compliance policy guide, a document that reflects their current thinking on this topic of therapeutic pet food diets. It directs FDA staff and industry on how the agency intends to use its enforcement discretion. At issue is the leeway that allows these therapeutic diets to be regulated as "food," even though many FDA officials believe these diets  really act as "drugs" because of their intended effects.

Therefore, FDA intends to specifically address dog and cat food products that are labeled and/or marketed as a means to diagnose, cure, mitigate, treat, or prevent diseases. They are especially interested in looking at diets that are marketed as an alternative to approved animal drugs and those that make a specific disease claim.

For more information about this topic, see the link to the article published by the VIN News Service (1), as well as the FDA web site to read the draft compliance policy guide on this topic (2,3).

Hill's y/d Diet and the FDA

The FDA's draft compliance policy guide almost seems like an direct response to my past criticism about how the Hill's y/d diet has been marketed in this country. For over a year now, Hill's Pet Foods has heavily been promoting y/d as a first-line treatment for a disease (i.e, feline hyperthyroidism). According to the company marketing ads (see below), Hill's 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.

Based on their vigorous marketing program, the Hill's pet food company is highly recommending this diet as a hyperthyroid treatment, meant to replace the other time-proven therapies. They even provide guidelines for how to weaning the cats off of methimazole and transition them on to the y/d diet.

In other words, Hill's is marketing y/d more like a drug to treat hyperthyroid cats than a diet per se. Unfortunately for the practicing veterinarian, the company has not done the Phase II or III drug trials normally required to determine a "drug's" efficacy or safety.  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. We still need more real data, and all we have now are a few abstracts that were published over a year ago (6-7).

Because Hill's says that y/d is not a drug (although it's certainly being marketed as one), the company is not required to do any long-term safety studies, and it's fairly clear that they have no intention of paying to have them done. Maybe the FDA can change some of that, or at least make Hill's modify and deflate their marketing claims.

References

1. VIN News Service. FDA poised to tighten oversight of therapeutic pet foods. September 14, 2012. 
2. FDA web site. Inspections, Compliance, Enforcement, and Criminal Investigations. Manual of Compliance Policy Guides.
3. FDA web site.  Draft Compliance Policy Guide: Labeling and marketing of nutritional products intended for use to diagnose, cure, mitigate, treat, or prevent diseases in dogs and cats. 
4. Hill's Pet Nutrition website. Prescription Diet y/d Feline Thyroid Health. 
5. 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.
6. 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.
7. 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.

Hyperthyroid Cats, Cantaloupe, and Hill's y/d Diet

Would you know if it is okay to feed cantaloupe to a hyperthyroid cat being managed with the low iodine y/d diet?

The owner feels that their cat is tired of the food and would like to give him a treat. The cat absolutely LOVES cantaloupe. I called Hill's but they didn't know if cantaloupe would interfere with the effectiveness of the diet.

My Response

The iodine content of food depends on the iodine content of the soil in which it is grown (1,2). Cantaloupe is often grown in iodine-rich soil (as all other crops and fruit), which unfortunately would compromise the effectiveness of the y/d diet. This case represents a common problem that we have with the y/d diet (3,4), which works to lower serum T4 concentrations by severely restricting the cat's iodine intake, thereby reducing the amount of thyroid hormone the thyroid tumor can secrete (5-7).

First of all, it's not the most tasty cat food on the market. Secondly, if y/d is going to continue to control the cat's hyperthyroid state, we can't feed the hyperthyroid cat any other cat food or treats that contain iodine or the y/d diet will fail and the hyperthyroidism will relapse.

My Bottom Line

So the bottom line is this: if the cat doesn't like the taste of the y/d, dietary management is not likely to be effective. Remember, if you switch this cat over to medical treatment with methimazole or, even better yet, use radioiodine or surgery to "cure" the hyperthyroid state, you can feed that cat whatever he wants to eat. And isn't that the way cats deserve to be fed, anyway?

References:

1. Yun AJ, Doux DJ. Iodine in the ecosytem: an overview. In: Preedy VR, Burrow GN, and Watson RR (eds). Comprehensive Handbook of Iodine.  Nutritional, Biochemical, Pathological, and Therapeutic Aspects. Academic Press, Elsevier, London 2009; 119-124. 
2. Hetzel BS, Wellby ML. Iodine. In: Handbook of Nutritionally Essential Mineral Elements, O'Dell BL, Sunde RA (Eds) Marcel Dekker, Inc. 1997;557-582.
3. Hill's Pet Nutrition website. Prescription Diet y/d Thyroid Feline Health (Dry). 
4. Hill's Pet Nutrition website. Prescription Diet y/d Thyroid Feline Health (Canned). 
5. Melendez LM, Yamka RM, Forrester SD et al. Titration of dietary iodine for reducing serum thyroxine concentrations in newly diagnosed hyperthyroid cats [abstract]. Journal of Veterinary Internal Medicine 2011;25:683.
6. Melendez LM, Yamka RM, Burris PA.Titration of dietary iodine for maintaining serum thyroxine concentrations in hyperthyroid cats [abstract]. Journal of Veterinary Internal Medicine 2011;25:683.
7. Yu S, Wedekind KJ, Burris PA, et al. Controlled level of dietary iodine normalizes serum total thyroxine in cats with naturally occurring hyperthyroidism [abstract]. Journal of Veterinary Internal Medicine 2011;25:683-684.

Transitioning Hyperthyroid Cats from Methimazole to Hill’s y/d: If It Ain’t Broke, Don't Fix It!

My patient is a 15-year old, F/S, DSH cat with a 2-year history of hyperthyroidism. Her thyroid values had been very well controlled on methimazole. However, she was becoming a “pain” to pill daily, and her methimazole dosage had recently increased from 2.5 mg to 5.0 mg per day. She has a past history of diabetes and had been in remission for 3 years on a low-carbohydrate, high-protein diet (dry Purina DM, ½ cup per day). She is a dry food addict and refuses to eat any canned cat food.

When Hill’s y/d came out, I thought that it was the perfect solution for this cat. Although she didn’t appear to like the y/d during the first week, she was eating it fairly well by the second week. Her methimazole dosage was completely phased out over the course of two weeks. I rechecked her serum T4 concentration at 4 and 8 weeks after starting the y/d and her T4 values were 3.9 μg/dl and 3.5 μg/dl, respectively (both in the upper end of the reference range).

My concern is that this cat has become ravenous, constantly begging for more food. The owner has fed the dry y/d in the amounts recommended by Hill’s (½ cup per day) and has even increased the amount fed to the cat. However, the cat doesn’t always finish the y/d she is fed and still cries for more food (obviously, she wants to eats something else).

The cat is starting to look quite emaciated, losing 2 pounds and a large amount of muscle mass over the 8 weeks she has been on the y/d diet. Her last serum glucose concentration was also higher than I’d like (at 210 mg/dl), although not high enough for me to diagnose overt diabetes and start insulin treatment once again.

Because of the cat’s clinical response, I decided to take her off the y/d and restart the methimazole and her regular food. She has only been back on the Purina DM for two weeks but already looks much better and has regained a pound. She certainly is acting much happier and is more content. The constant begging and crying have stopped. Both the serum concentrations of T4 (2.2 μg/dl) and glucose (125 mg/dl) are lower than they were on the y/d.

Is this a problem Hill's is seeing with the y/d? I feel like I did more harm than good to my cat by switching her over from methimazole to the y/d. What are your thoughts on this food?

My Response

In the future, you may want to follow the advice of the adage (1), "If it ain’t broke, don't fix it!”

Let me first state that most cats that are treated with Hill’s y/d diet respond better than your cat did (it would be difficult to have a worse response!). But this case does bring up the issue that many cats will not respond completely to this diet, and some cats, such as this patient, will completely fail to respond.

And remember that even if a cat does respond adequately, the diet must be continued as the sole food source for the rest of the cat’s life to maintain euthyroidism (2). With y/d, the underlying cause of a cat’s hyperthyroidism will never be cured; rather, the hyperfunctional thyroid tumor(s) remains and may continue to grow larger with time (3,4).

So what happened to your cat to cause the failure of y/d? Well, it looks like a number of issues contributed to the problems with rapid weight loss, muscle wasting, and recurrence of hyperglycemia that this cat experienced while being fed Hill’s y/d diet.

Poorly controlled hyperthyroidism on the y/d diet
First of all, the serum T4 concentration in this hyperthyroid cat only decreased into the high-normal range. If you had measured a free T4 concentration in this cat when fed the y/d, I can guarantee that the free T4 value would have been quite high. No matter what treatment is given, it’s important to lower the total T4 concentration into the mid-normal range to ensure that the cat’s free T4 is also normalized and whole-body euthyroidism is restored (3,5,6).

So persistent and poorly controlled hyperthyroidism certainly contributed to the worsening of this cat’s weight loss and muscle wasting, despite the increased appetite in this cat. Remember hyperthyroidism accelerates the metabolic rate and body’s energy expenditure (7,8); these cats are burning up their food calories faster than they can consume their daily meals (5,6,9). In some cats, as in your patient, the body consumes its own muscle tissue to get the protein it needs to sustain its carnivorous life.

Decreased caloric intake on the y/d diet
In addition to the poorly controlled hyperthyroidism, it also appears that your cat was eating significantly fewer calories when fed the y/d. If we compare the caloric content of Purina DM to Hill’s y/d, we find that ½ cup of DM provides almost 300 kcal whereas ½ cup of y/d provides only 259 kcal (2,10). This 40 kcal per day might not seem like much, but that’s a 15% decrease in the amount of daily calories ingested!

Another important point in this cat is the fact that she did not find the y/d particularly palatable, and therefore did not eat more of the y/d food to compensate for the lower-caloric food. Remember, a few cats may actually like the y/d, but almost all of the cats I have seen on the diet would much rather eat another type of food if given the choice (11).

Decreased protein intake on y/d diet
In addition to caloric density, Hill’s y/d is also much lower in protein compared to the Purina DM (36% vs 58% on a dry matter basis) (2,10).

Remember that protein is the primary macronutrient responsible for maintenance of muscle mass. Restoring and preserving any remaining muscle tissue in cats treated for hyperthyroidism depends upon the cat consuming a diet with sufficient amounts of high-quality protein.

The lower protein intake of Hill’s y/d, together with the lower caloric intake, both contributed to the muscle breakdown and rapid loss of muscle mass in this cat when fed the diet. If this cat had been able to increase the daily amounts of y/d ingested, this may have lessened or prevented the loss of muscle mass that developed in the cat (12,13).

Higher carbohydrate intake on y/d diet
It is well accepted by most practicing veterinarians who specialize in feline medicine that a low-carbohydrate diet is a mainstay in the treatment of diabetes mellitus, especially if remission of the diabetic state is the goal. Feeding a low-carbohydrate diet will improve insulin sensitivity, reduce or eliminate the need for exogenous insulin, and help stabilize glucose metabolism in these cats (14-16).

If remission is achieved, it is very important to continue the low carb diet. In this cat, remission of diabetes was maintained for years by feeding Purina DM diet, which is relatively low in carbohydrates (i.e., 15% on a dry matter basis). Most feline veterinarians like to feed even lower levels of carbs (< 10%) to cats with active diabetes (14,15). To achieve these low carbohydrate levels, we must feed a canned food —none of the available dry cat foods contain <10% carbohydrates. If the diabetic cat goes into remission, we recommend maintaining a restricted carbohydrate diet for life to help prevent relapse of the diabetic state.

In contrast, Hill’s dry y/d diet is relatively high in carbs (i.e., 29% on a dry matter basis), much higher than the 15% found in Purina dry DM diet (2,10). This increased carbohydrate load likely contributed to this cat’s hyperglycemia and probably would have led to recurrence of overt diabetes mellitus if the y/d diet had been continued.

Hill’s y/d and the hyperthyroid cat: my bottom line

Overall, this case illustrates a number of potential problems with y/d for managing cats with hyperthyroidism.

1. First of all, the diet may not be totally effective in lowering serum total and free T4 values.
2. Secondly, the diet is not very palatable to many cats, and some cats either refuse to eat the diet or fail to eat enough.
3. Thirdly, because the y/d diet is relatively low in protein, weight loss and muscle wasting may result if the hyperthyroid cats fail to ingest adequate amounts of the diet to provide the calories and protein they need to restore normal body weight and muscle mass.
4. Finally, because y/d is a high-carbohydrate diet, this is certainly the worst type of diet to feed to a diabetic cat or a cat in diabetic remission (14-16). These cats should be ideally be fed a low carb canned diet, with higher levels of protein or fat.

For those of you who have read my other posts concerning the Hill’s y/d diet, you know that I’m not a big fan. Of course, we all care for hyperthyroid cats in which no other treatment option is found acceptable for the owner. But most cats, at least in the long-term, will do better with our other treatment options, especially definitive therapy that really addresses the cause — that is, the thyroid adenoma or carcinoma causing the hyperthyroid state.

At least for owners who are willing to do the best for their cat, isn’t it most logical to cure the thyroid disease rather than trying to control it with a diet that is too low in protein, too high in carbohydrates, and chock-full of grains that a cat would never eat in the wild? Would you really want your own cat to eat this diet when the long-term consequences are still not even known?

References:

1. Wikipedia.org. Bert Lance. Quote in Nation’s Business, May 1977. 
2. Hill's Pet Nutrition website. Prescription Diet y/d Thyroid Feline Health.
3. Insights into Veterinary Endocrinology blog. Treating Hyperthyroid Cats with an Iodine Deficient Diet (Hill's y/d): Does It Really Work? September 24, 2011. 
4. Peterson ME, Broome MR: Thyroid scintigraphy findings in 917 Cats with hyperthyroidism. Journal of Veterinary Internal Medicine 2012; in press.
5. Mooney CT, Peterson ME: Feline hyperthyroidism, In: Mooney CT, Peterson ME (eds), Manual of Canine and Feline Endocrinology (Fourth Ed), Quedgeley, Gloucester, British Small Animal Veterinary Association 2012; 92-110.
6. Baral RM, Peterson ME. Thyroid gland disorders: Hyperthyroidism & hypothyroidism. In: Little SE, ed. The Cat: Clinical Medicine and Management. St. Louis: Elsevier Saunders 2012:571-592.
7. Morrison WL, Gibson JN, Jung RT, et al. Skeletal muscle and whole body protein turnover in thyroid disease. European Journal of Clinical Investigation 1988;18:62–68.
8. Riis AL, Jørgensen JO, Gjedde S, et al. Whole body and forearm substrate metabolism in hyperthyroidism: evidence of increased basal muscle protein breakdown. American Journal of Physiology: Endocrinology and Metabolism 2005; 288:E1067-1073.
9. Little SE: Evaluation of the senior cat with weight loss. In: Little SE, ed. The Cat: Clinical Medicine and Management. St. Louis: Elsevier Saunders 2012:1176-1181.
10. Purina Veterinary Diets website. DM Dietetic Management Feline Formula. 
11. Peterson ME.  Anorexia in a hyperthyroid cat on Hill’s y/d. Insights into Veterinary Endocrinology blog. February 7, 2012.  
12. Wakshlag JJ. Dietary protein consumption in the healthy aging companion animal. Proceedings of the Nestlé Purina Companion Animal Nutrition Summit: Focus on Gerontology. St. Louis, MO. 2010, pp. 32-39.
13. Peterson ME. Can Increasing the Amount of Fat or Carbohydrate in a Cat's Diet Compensate for Low Protein Intake? Insights into Veterinary Endocrinology blog. December 22, 2011. 
14. Frank G, Anderson W, Pazak H, et al. Use of a high-protein diet in the management of feline diabetes mellitus. Veterinary Therapeutics 2001;2:238-246.
15. Rand JS. Feline diabetes mellitus. In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology, Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association 2012:133-147.
16. Baral RM, Little SE. Endocrine pancreatic disorders: Diabetes mellitus, gastrinoma, and insulinoma. In: Little SE, ed. The Cat: Clinical Medicine and Management. St. Louis: Elsevier Saunders 2012:547-571.

Q & A: Persistent Hyperthyroidism in a Cat Treated with Hill's y/d

My patient is a 12-year old male spayed Siamese cat who has been hyperthyroid for 3 years. Over this time, his thyroid nodules have gradually increased in size and his methimazole dosage has increased from 2.5 mg once a day to 15.5 mg twice a day. Despite this large dose of methimazole, his serum T4 value remained in the high-normal to slightly hyperthyroid range.

After looking over the blood work and dosage and talking to the owner, we decided to try the new Hill's y/d diet. The cat has been on y/d food for over 3 months and her last serum T4 level was high-normal at 3.8 μg/dl. I usually prefer the values to be within the lower end of the reference range, so this seems to high for this cat.

Should I continue the y/d food and recheck or consider adding back the methimazole again? Why isn't this cat responding to either the methimazole or y/d diet?

My Response:

First of all, we must never forget that all cats with hyperthyroidism have a hyperfunctional thyroid tumor (1-6). These tumors are almost always benign at time of diagnosis, but they will usually continue to grow progressively larger when treated medically with either methimazole or carbimazole.

Although we don't know how the growth of these feline thyroid tumors will response to an iodine deficient diet, such as Hill's y/d, I would predict that the tumor will continue in its progressive growth pattern (1).

The fact that neither the methimazole or Hill's y/d is controlling the hyperthyroidism as well as you would expect is probably related to the fact that, after 3 years, the volume of this cat's thyroid tumor tissue is quite large. You could continue the y/d diet and reinstate a small dose of methimazole to the cat's treatment regimen, but you would need to monitor the cat's thyroid function very carefully over the next few weeks to ensure that hypothyroidism does not develop on the concomitant therapy.

Even if you can control the hyperthyroidism now, your cat could live a long time (she is a Siamese, after all). As she ages, the thyroid tumor will continue to grow and may transform into a thyroid carcinoma (7,8). In my studies, less than 2% of recently diagnosed hyperthyroid cats had thyroid carcinoma, whereas up to 20% of cats treated medically for longer than 4 years had evidence of thyroid carcinoma on thyroid imaging (7).

If this was my patient, I'd either do surgery or radioiodine to cure the cat's hyperthyroidism rather than trying to manage it with Hill's y/d or methimazole for the rest of her life. She is already suffering from a severe case of hyperthyroidism, which will only worsen with time. In the long run, a definitive treatment would be the wisest (and most cost effective) means of treating this relatively young cat.

And again, she is a Siamese and most cats of that breed, when properly managed, seem to live almost forever!

References:

1. Peterson ME, Ward CR. Etiopathologic findings of hyperthyroidism in cats. Veterinary Clinics of North America Small Animal Practice 2007;37:633-645. 
2. Baral R, Peterson ME. Thyroid gland disorders. In: Little, S.E. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders 2012; 571-592. 
3. Peterson ME: Hyperthyroidism, In: Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat (Fifth Edition). Philadelphia, WB Saunders Co. 2000; pp 1400-1419.
4. Peterson ME: Hyperthyroidism in cats. In: Melian C (ed): Manual de Endocrinología en Pequeños Animales (Manual of Small Animal Endocrinology). Multimedica, Barcelona, Spain, 2008, pp 127-168.
5. Mooney CT, Peterson ME: Feline hyperthyroidism, In: Mooney C.T., Peterson M.E. (eds), Manual of Canine and Feline Endocrinology (Fourth Ed), Quedgeley, Gloucester, British Small Animal Veterinary Association, 2012; in press. 
6. Peterson ME: Hyperthyroidism in cats, In: Rand, J (ed), Clinical Endocrinology of Companion Animals. New York, Wiley-Blackwell, 2012; in press.
7. Peterson ME, Broome MR. Thyroid scintigraphic findings in 917 cats with hyperthyroidism. Journal of Veterinary Internal Medicine 2012; in press.
8. Hibbert A, Gruffydd-Jones T, Barrett EL, et al. Feline thyroid carcinoma: diagnosis and response to high-dose radioactive iodine treatment. Journal of Feline Medicine and Surgery 2009;11:116-124. 

Feeding Hill's y/d and Feline Immune Function

Is there a potential problem with the low level of iodine in y/d possibly reducing a cat's immune response?

I asked our Hill's representative who told me that the iodine content of y/d is not that low and it's not even deficient in iodine content — it's just lower than other commercial diets. The Hill's rep told me that they wouldn't worry at all about immune function or deficiencies in cats fed this diet, even for years.

I had heard that iodine played a role in immune function. What are your thoughts on this matter?

My Response:

Is Hill's y/d an iodine deficient diet?
The 2009 study by Wedekind, et al (1), in a study supported by Hill's Pet Nutrition, clearly showed that the iodine requirement in normal cats fed a corn gluten meal-corn based diet (similar to the ingredients in Hill's y/d) was 0.46 mg I/kg of diet. This amount of dietary iodine supplies about 20-25 μg of daily iodine to the average-sized cat.

This iodine requirement of 0.46 mg/kg of diet is more than 2-fold higher than the iodine content of Hill's y/d, which contains only 0.2 mg I/kg of diet (2,3). The y/d diet provides only about 10 μg of iodine to the average sized cat each day; again, less than half of the minimum daily iodine requirement published in the recent study by Wedekind (1).

So the Hill's folks and I can debate whether y/d is truly iodine deficient or not, but the published study that they supported (1) provides strong evidence that y/d clearly is an iodine-deficient diet. The Hill's folks get around this by calling it an iodine-restricted diet (2,3), but I would rather be completely transparent and label the diet for it what it is!

Iodine deficiency and immunity
Based on a number of studies in man and other species, it's clear that iodine has many extra-thyroidal functions in the body. Iodine plays an important role in the immune response (4-7). It also has anti-inflammatory and anti-oxidative actions (8-12).

Iodine deficiency in humans is associated with an increased prevalence of infectious diseases. In one study of adolescent girls and women in Bangladesh, where iodine deficiency is commonplace, the presence of iodine deficiency was associated with an increased risk of eye infections, ear infections, pneumonia, and diarrhea/dysentery (13). Childhood survival is also threatened by iodine deficiency, in part due to infectious complications (14).

Remember that the biggest concern in these iodine deficient populations is not infection, however, but rather the goiter, hypothyroidism, cretinism and other developmental defects that develop. Inasmuch as one third of the world' population are iodine deficient, correcting this publish health problem has become the goal of a massive global campaign (15,16).

Iodine supplementation as a therapy for infectious diseases
Before the discovery of antibiotics, iodine was used for a wide variety of ailments in the 19th and early part of the 20th centuries, especially for syphilis and chronic lung disease (17,18). The Nobel laureate Albert Szent Györgi (1893–1986), the physician who discovered vitamin C, wrote in his book (19): “When I was a medical student, iodine in the form of potassium iodide was the universal medicine. Nobody knew what it did, but it did something and did something good.”

In accord with that, it was recently suggested that iodine therapy might play a useful role in treating AIDS infections in both humans, as well as cats (20).

Hill's y/d and immune function in cats
So based on what we know in other species, I am indeed worried about y/d resulting in a decreased immune response in cats fed this diet for prolonged periods. Remember that in people, world authorities are doing all that they can do to prevent and correct iodine deficiency (15,16). No one would ever try to induce iodine deficiency in any human patients, even if they had thyroid disease.

So Hill's has succeeded in doing something that has never done before— that is, to make a diet, that fed chronically to our patients, will induce an iodine-deficient state. Even if thyroid function remains normal, that does not mean that the cat's whole body iodine levels are not deficient and that their immune function is not compromised.

Remember that Hill's has not provided us with any research data on immune function of any of the cats fed y/d in their colony for years. I have heard of a few hyperthyroid cats, however, that developed upper respiratory tract or urinary tract infections while being fed this diet — is this due to a suppressed immune function or just coincidence that they were eating a diet low (or deficient) in iodine? We just don't know. But I find it strange that these older cats would suddenly develop URI when they have not had a history of respiratory disease.

In my opinion, well-designed long-term studies of cats fed this diet need to be done to address this issue before any conclusive statements can be made. Again, Hill's claims that such studies would be difficult and expensive to do — but remember, if this diet had required FDA approval as a drug (and y/d really is a powerful drug if you stop and think about it), that is exactly what the FDA would require the company to do before release of this therapeutic diet to the market.

Bottom Line
If you decide to use this diet for management of your hyperthyroid cats, you should be on the look-out for signs of a suppressed immune response. If signs of infection do develop, the diet should be stopped and iodine supplementation given, and the hyperthyroidism should be treated with one of the other standard treatment methods (i.e, radioiodine, methimazole, or surgical thyroidectomy).

Because of this potential issue with immune function and iodine deficiency, I feel strongly that this is another reason that the Hill's y/d diet should never be fed chronically to a euthyroid cat that does not have hyperthyroidism.  The suggestion that feeding an iodine deficient diet to clinically normal cats is "safe" is simply contrary to all reason or common sense, considering what we know about iodine deficiency in man.

References:

1. 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. 
2. Hill's Pet Nutrition website. Prescription Diet y/d Thyroid Feline Health (Dry). 
3. Hill's Pet Nutrition website. Prescription Diet y/d Thyroid Feline Health (Canned).
4. Marani L, Venturi S, Masala R. Role of iodine in delayed immune response. Israeli Journal of Medical Science 1985;21:864. 
5. Simmons SR, Karnovsky ML. Iodinating ability of various leukocytes and their bactericidal activity. Journal of Experimental Medicine 1973;138:44-63.
6. Weetman AP, McGregor AM, Campbell H, et al. Iodide enhances IgG synthesis by human peripheral blood lymphocytes in vitro. Acta Endocrinologia 1983;103:210-215. 
7. Venturi S, Venturi M. Iodine, thymus, and immunity. Nutrition 2009;25:977-979.
8. Miller DW. Extrathyroidal benefits  of iodine. Journal of American Physicians and Surgeons 2006;11:106-110. 
9. Ware CM, Wishner LA. The lipid antioxidant properties of iodine compounds. Lipids 1968;3:182-183.
10. Smyth PP. Role of iodine in antioxidant defense in thyroid and breast disease. Biofactors 2003;19:121-130.  
11. Patrick L. Iodine: deficiency and therapeutic considerations. Alternative Medicine Review 2008;13:116-127. 
12. Soriguer F, Gutierre-Repiso C, Rubio-Martin E, et al. Iodine intakes of 100-300 μg/d do not modify thyroid function and have modest anti-inflammatory effects. British Journal of Nutrition 2011;25:1-8.
13. Harun-Or-Rashid M, Khatun UF, Yoshida Y, et al. Iron and iodine deficiencies among under-2 children, adolescent girls, and pregnant women of Bangladesh: association with common diseases. Nagoya Journal of Medical Science 2009;71:39-49.
14. Cobra C, Muhilal, Rusmil K, et al. Infant survival is improved by oral iodine supplementation. Journal of Nutrition 1997;127:574-578.
15. Zimmermann MB. Iodine deficiency. Endocrine Reviews 2009;30:376-408.
16. International Council for the Control of Iodine Deficiency Disorders. www.iccidd.org
17. The Encyclopaedia Britannica. Vol 14. 11th ed. New York. Encyclopaedia Britannica Company; 1911:726.
18. Iodine. Manual of Therapeutics. Parke, Davis & Company. Detroit, Michigan 1919;360-361.
19. Szent-Györgyi A. Bioenergetics. New York, Academic Press; 1957:112.
20. Mamo JCL, Naissides M. Could iodine be effective in the treatment of human immunodeficiency virus and AIDS-associated opportunistic infections. International Journal of Infectious Diseases 2005;9:292-293. 

Q & A: Switching a Hyperthyroid Cat From Hill's y/d Back To Methimazole

I have a 7-year old female spayed Siamese cat that has been on Hill's y/d food for the past 2 months. The cat's thyroid levels have not come down (still > 15 μg/dl) and she is miserable on the food. She acts like she's starving (possibly from the uncontrolled thyroid) and is trying to steal food from the owner.

I am discontinuing the food but was wondering if I need to wait a certain amount of time before starting her back on methimazole?

My Response:

I've heard the same story from many cat owners and veterinarians. The y/d just doesn't appear to look and taste very appetizing to many cats (the food certainly looks pretty gross to me, but I must admit — I haven't tasted it!).

If the cat's serum T4 value is still high now, I'd switch the cat to a good diet (higher in protein, lower in carbs) that she wants to eat and start methimazole now.

• A 7-year old Siamese could live a very long time, possibly another 15 years! I'd talk to the owners about the following facts when you discuss how to treat the cat's hyperthyroidism (1-5): 
• This cat, like all hyperthyroid cats, has a thyroid tumor
• The thyroid tumor and hyperthyroidism will never go into spontaneous remission
• The thyroid tumor will continue to grow larger with time
• In some cats treated long term medically, the benign tumor will transform into a malignant thyroid carcinoma. In my studies, the incidence of thyroid carcinoma is above 20% in cats treated medically for longer than 4 years (6).

The bottom line:
If this was my own cat, I'd either do surgery or radioiodine to cure the cat's hyperthyroidism rather than trying to manage it with an iodine deficient diet (Hill's y/d) or methimazole for the rest of her life (1-5,7,8). She is already suffering from a severe case of hyperthyroidism, which will only worsen with time.

In the long run, a definitive treatment would be the wisest (and most cost effective) means of treating this relatively young cat.

References & Suggested Reading:

1. Baral R, Peterson ME. Thyroid gland disorders. In: Little, S.E. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders 2012; 571-592. 
2. Peterson ME: Hyperthyroidism, In: Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat (Fifth Edition). Philadelphia, WB Saunders Co. 2000; pp 1400-1419.
3. Peterson ME: Hyperthyroidism in cats. In: Melian C (ed): Manual de Endocrinología en Pequeños Animales (Manual of Small Animal Endocrinology). Multimedica, Barcelona, Spain, 2008, pp 127-168.
4. Mooney CT, Peterson ME: Feline hyperthyroidism, In: Mooney C.T., Peterson M.E. (eds), Manual of Canine and Feline Endocrinology (Fourth Ed), Quedgeley, Gloucester, British Small Animal Veterinary Association, 2012; in press. 
5. Peterson ME: Hyperthyroidism in cats, In: Rand, J (ed), Clinical Endocrinology of Companion Animals. New York, Wiley-Blackwell, 2012; in press.
6. Peterson ME, Broome MR. Thyroid scintigraphic findings in 917 cats with hyperthyroidism. Journal of Veterinary Internal Medicine 2012;26:754.
7. Peterson ME: Radioiodine treatment for hyperthyroidism. Clinical Techniques in Small Animal Practice 2006;21:34-39.
8. Peterson ME: Radioiodine for hyperthyroidism. In: Bonagura JD, Twedt DC (eds): Current Veterinary Therapy XIV. Philadelphia, Saunders Elsevier, 2008, pp 180-184.

Link to My Other Posts on the Hill's y/d Diet

Q & A: Anorexia in a Hyperthyroid Cat on Hill's y/d

I have a 12-year old female DSH cat with hyperthyroidism that we have been managing with the new Hill's y/d diet. The cat was eating both the canned and dry y/d, and the serum T4 fell from 7.0 μg/dl to 3.2 μg/dl after 2 months.

So everything was going along fine on y/d without any other medication. But now the cat has completely stopped eating for the last 2 days. Other than the cat's palpable thyroid tumor and low body condition score, my physical examination was normal. Repeat routine blood work did not reveal any abnormalities.

So what should we do in this situation? The owner suspects it's an issue with the taste of the y/d and thinks that she would eat her "regular" cat food.

Is there something else to do first before doing a further workup searching for a concurrent disease? If we give her another food, will she become hyperthyroid once again?

My Response:

This is one of the major disadvantages we have when relying on a extremely low iodine diet (Hill's y/d) to control a cat's hyperthyroidism.  Let's face it — Hill's y/d isn't the tastiest cat food on the market, and most cats (if not all) would prefer to eat another type of diet.

But more importantly is the fact that almost all cats, as they age, will develop episodes of partial to complete anorexia secondary to nonthyroidal illness. In these sick cats, we often first tempt them to eat with different foods (fish-flavored, etc) or use recovery-type diets before embarking on a major workup for a concurrent disease. However, feeding these cats any other food but y/d increases their iodine intake, and will result in relapse of the cat's hyperthyroid state.

How long to relapse on the y/d diet is stopped? Well, that depends on a number of factors including the following:

• The size of the hyperthyroid cat's thyroid tumor (which will continue to grow on the y/d diet).
• The magnitude of the cat's original serum T4 value (i.e., higher T4 values reflect an increase in severity of hyperthyroidism, with a larger thyroid tumor size).
• The time on the y/d diet.
• How low the cat's T4 fell on the y/d diet, which reflects how iodine depleted the cat's thyroid tumor became on the diet. In other words, if the serum T4 decreased into low-normal range of on the y/d, we would expect the cat to remain euthyroid longer than if the T4 only fell to upper limit of the reference range, as in this cat.

In any case, we know that the serum T4 will increase again, once the y/d is not fed exclusively. You must continue this iodine deficient diet for the rest of the cat's life for this diet to continue to manage the hyperthyroidism. So we would want to get them back on y/d and off the "temporary" foods as soon as possible. If they remain on a diet other than y/d for any length of time (certainly longer than 1 to 2 weeks), it's likely that they will show relapse and T4 will have to be monitored.

Remember that once they relapse, it's going to take a few weeks feeding the y/d diet exclusively for the serum T4 to again fall into the euthyroid range.

Bottom Line:

Veterinarians have to be prepared for the fact that many, if not all, senior hyperthyroid cats will develop concurrent diseases as they age, some of which will require management with a diet other than Hill''s y/d. This is one of the major downsides of using this diet management for the long-term control of cats with hyperthyroidism.

Owners must be made aware of the fact that another treatment method might be needed if the cat's disease state dictates the need for another diet plan.

Link to My Other Posts on the Hill's y/d Diet

Believe The Hype? Hill's Latest Marketing Slogan for the y/d Diet

I attended the North American Veterinary Conference (NAVC) in Orland Florida this week, where I presented a number of lectures on a variety of endocrine topics (complete list of topics on my website). 

One lecture that I had agreed to present 9 months ago was part of a Hill's seminar on diagnosis and treatment of feline hyperthyroidism. The topic that I had agreed to present (which I did present last Monday morning on January 16th), was entitled "Feline Hyperthyroidism: Risk Factors and Diagnosis." This was arranged before Hill's iodine deficient y/d diet had been released, so the intense marketing campaign that we have seen over the last 3 months had not yet begun.

The day before I traveled to the NAVC conference, I received an email from Hill's with the above ad, promoting the hyperthyroid seminar that I would soon be a part of — to be honest, I was shocked and rather embarrassed that I was to be a part of this y/d promotion.

Once I arrived in Orlando, the slogan, Believe The Hype was posted as a prominent banner almost everywhere that one looked. Again, I was feeling more and more uncomfortable that I was to be included as part of this "hype,"especially since I'm not convinced that this diet is even safe to use, based on the evidence.  (To see my past posts which discuss the y/d diet, click here.)

Remember that we have yet to see any referred scientific publications with the complete data that answer all of our questions. The Hill's research team certainly hasn't responded to most of my questions that I've brought up about y/d in my blogs.

Defining the Term, Hype

After thinking about "Believe The Hype" banner and discussing the matter over dinner with friends, someone asked the obvious question —What does the word hype really mean, anyway?

Well, according to the Merriam-Webster Dictionary, the word, when used as a noun as it is in the slogan, has two possible meanings:

1. deception, put-on
2. publicity; especially: promotional publicity of an extravagant or contrived kind 

And according to an online dictionary (dictionary.com), the word hype has three meanings, all similar to those found in the Merriam-Webster  source:

1. exaggerated publicity; hoopla
2. an ingenious or questionable claim, method, etc., used in advertising, promotion, or publicity to intensify the effect
3. a swindle, deception, or trick

So What Is Hill's Implying with the Believe The Hype Slogan?

At face value, is the marketing division at Hill's actually asking us to believe that the information they have provided about the y/d diet is all hype? Remember that the word is defined as exaggerated, ingenious or questionable claims, put-ons, or tricks!

Interesting thought, isn't it.

Personally, I find the slogan to be "over-hyped" — unnecessarily exaggerated to the point of overkill. Why don't they present the hard evidence, answer the real questions that we all have, and forget this foolishness?

My Bottom Line

We all need to remember that this marketing campaign for the Hill's y/d diet, as well as the marketing ads for the multitudes of products that we get bombarded with every day, is all about hype.

As veterinarians and advocates for our feline patients, our job is to dig below this exaggerated hype and find the real science (if any) behind this sensational publicity. In the case of y/d, Hill's has created much more hype than usual or really necessary (at least in my opinion).  If half of this money spent on this marketing campaign would be directed toward research on feline hyperthyroidism, we may be able to find the cure for this disease!

I know that it is tempting to get taken in with all marketing of new products, especially y/d. My goal in writing these blog posts, the way I see it, is to try to bring everyone back to earth and make the practicing veterinarian think about the possible long-term implications of feeding y/d to cats. That's what I have tried to do over the past few weeks and will continue to do as needed in the future.

Hill's y/d diet is different than all of the other commercial pet foods on the market because they are promoting y/d as a treatment for a disease — in other words, Hill's is marketing y/d more like a drug than a diet per se.  In that regard, I believe that they need to do the studies to ensure that this diet is safe, as well as effective, just as any pharmaceutical company would have to do for FDA approval.  From what I've heard, however, no further safety studies are planned simply because they are not required to do them.

But is that the "right" thing to do, just because the diet isn't regulated as a drug by the FDA? Or is it all about selling as much cat food as possible to keep the shareholders happy?

Can Increasing the Amount of Fat or Carbohydrate in a Cat's Diet Compensate for Low Protein Intake?

As I discussed in a recent post on Optimal Protein Requirements for Older Cats and Cats with Hyperthyroidism, energy requirements sharply and progressively increase in older cats starting at 10 to 12 years of age (1-3). If daily caloric intake is not increased, progressive weight loss will result, due in large part to the loss of lean body mass (i.e., muscle mass), a phenomenon referred to “sarcopenia” of aging (4-7).

In addition to this increased caloric intake, older cats also require higher amounts of protein to maintain protein reserves compared with younger adult cats (3, 8-11). As cats age, they absorb and metabolize protein less efficiently (10). Therefore, it’s extremely important to feed high-quality protein (i.e., animal source rather than grain-based), as well as an adequate quantity of protein to aging cats.

Animals derive energy from the oxidation of the macronutrients carbohydrate, fat, and protein (12). Most animals, including rats and humans, generally adapt to the diet being fed and can oxidize whatever fuel mixture is contained in their prevailing diet (13,14). This enables most animals (especially omnivores) to use widely differing diet compositions to satisfy their energy requirements.

A number of veterinarians have contacted me over the last few weeks with concerns about the potential problems associated with feeding a high protein diet to the geriatric cat, especially in those cats with kidney disease. Basically, the questions come down to the following:

• If animals can adapt their energy intake based on a wide variety of feeding regimens, why can’t we just increase the amounts of fat and carbohydrate fed to compensate for the increasing energy requirements in our senior (and hyperthyroid) cats? Won't that help prevent loss of muscle mass?
• But can cats as obligate carnivores adapt to the same extent?

In this post, my mission is to review energy and protein metabolism in cats. I will attempt to explain why, unfortunately, increasing the amount of fat or carbohydrate fed to an older or hyperthyroid cat generally cannot compensate for a diet deficient in an optimal protein content.

Overview of the Body's Energy Production (Nutritional Biochemistry 101)

Fig. 1: Pathways of
intermediary metabolism

Let's start with a brief review of nutritional biochemistry. If you are a practicing veterinarian like myself, it's highly likely that you may not remember all of the metabolic pathways an animal uses for energy production.

The initial biochemical reactions by which energy is derived from carbohydrates, fats, and proteins are different. However, all 3 macronutrients eventually go through a final common pathway for energy generation called the citric acid cycle — also known as the tricarboxylic acid cycle (TCA) cycle or the Krebs cycle (Figure 1) (12,15).

Carbohydrates: Glucose derived from dietary carbohydrates is first oxidized through the glycolysis pathways to yield pyruvate and then acetyl-CoA. The acetyl-CoA is then oxidized in the citric acid cycle (12,15). High-energy electrons produced in the citric acid cycle enter the electron transport chain to generate adenosine triphosphate (ATP), which transfers its energy from chemical bonds to energy-absorbing chemical reactions within the cell (Figure 1).

Fats: Fatty acids from dietary fats are initially oxidized to acetyl-CoA by the beta-oxidation pathway, which then enter the citric acid cycle and subsequently generate ATP via oxidative phosphorylation in the electron transport system (Figure 1).

Figure 2: Protein catabolism

Protein: Once protein synthesis is maximized, excess amino acids can be used for energy by undergoing transamination and deamination. In oxidative deamination, an amino group is removed from the amino acid and converted to ammonia.

The remaining carbon skeleton from these deaminated amino acids (organic ketoacids) can be recycled to make nonessential amino acids, or they can be oxidized for energy (12,15). If used for energy, the catabolized amino acids enter either the glycolysis pathway or the citric acid cycle to ultimately form ATP in the electron transport system (Figure 1). The carbon skeletons of catabolized amino acids can also be converted to glucose or ketone bodies in the liver.

Ammonia is toxic to the body, so enzymes convert it to urea by addition of carbon dioxide in the urea cycle, which takes place in the liver. Urea can safely diffuse into the blood and then be excreted into the urine (Figure 2).

Interconversion of nutrient molecules: In metabolism, there commonly is interconversion of nutrient molecules. Excess glucose is stored as glycogen (glycogenesis); when glycogen stores are filled, glucose and amino acids are used to synthesize lipids (lipogenesis). Therefore, glycogen and adipose tissue both serve as long-term forms of energy storage in the body.

In contrast, amino acids are not "stored" in the body, other than that found in muscle and other structural proteins. Although amino acids can be converted to either fat or glucose, the opposite does not occur — fat and carbohydrates cannot be directly converted to amino acids to be made into protein (12-15).

Protein Structure, Functions & Metabolism

Proteins, from the Greek proteios meaning "first" (16), are important biological molecules that consist of string of amino acids linked together in sequence as polypeptide chains. Proteins vary in shape and size, some consisting of only 20-30 amino acids and others of several thousands (12,15).

Proteins are present in every living cell. In the skin, hair, cartilage, muscles, tendons, and ligaments, proteins hold together, protect, and provide structure to the body. As enzymes, hormones, antibodies, and globulins, they catalyze and regulate body chemistry. In addition, protein is required for growth and tissue repair, as well as for maintaining muscle mass and tone.

Essential and Nonessential Amino Acids
More than 20 amino acids are involved in the synthesis of protein in the body. Essential amino acids are those that cannot be formed in sufficient amounts to meet the requirements for growth and maintenance and must be supplied in the diet. Nonessential amino acids are those that the body can produce in sufficient amounts from other nutrients and metabolites and, thus, do not need to be supplied in the diet.

Even with the nonessential amino acids, however, fat and carbohydrates cannot be directly converted to amino acids to be made into protein (12,15). Although all mammals can synthesize 10 nonessential amino acids from precursor carbon skeletons (if adequate nitrogen and energy are available), there is no direct way that amino acids can be synthesized directly from either fat or carbohydrates.

Amino Acid Catabolism & Synthesis—Protein Turnover
Although essential amino acids are not stored as such in the body for any significant period of time, all body proteins are continuously being broken down and resynthesized in a process known as protein turnover (12,15,17). During protein turnover, some amino acids enter catabolic pathways and are permanently lost. Therefore, adequate amounts of high-quality dietary protein (containing all the essential amino acids) must be consumed each day to replace the both the essential and nonessential amino acids lost to catabolism.

Hypermetabolic states, such as hyperthyroidism or other illness, increase both protein turnover and nitrogen losses and therefore increase the daily protein requirements (18,19).

Protein as an Energy Source
Unlike fat or carbohydrate, protein cannot be stored as such in the body (other than as muscle protein itself).  In animals fed diets containing more protein than is needed, the extra protein is metabolized and used for energy (Figures 1 & 2).

In all species, but most importantly in cats (see below), ingested amino acids are converted to carbohydrates via gluconeogenesis (12,15,17, 20-22). This pathway is also used under starvation conditions to generate glucose and energy from the body's own proteins, particularly those found in muscle.

Factors That Determine How Dietary Proteins are Used

• All or None Rule: To make a certain protein, the necessary amino acids must be present in the cell in the right amounts, or the protein will not be made. Essential amino acids that are not used to make proteins are not stored.
• Adequacy of Caloric Intake:  If the diet fails to provide sufficient calories as carbohydrates and fats, proteins will not be synthesized; instead the ingested amino acids will be used as a source of energy.
• Nitrogen Balance:  Normally, the amount of protein synthesis is equal to the amount of protein breakdown (12,17). If there is more protein synthesis than breakdown, then we have a positive nitrogen balance (e.g., recovery from injury). If there is greater protein breakdown than synthesis, then there is a negative nitrogen balance (e.g, starvation, illness, hyperthyroidism).
• Hormonal Controls:  Anabolic hormones (e.g., insulin, growth hormone, sex hormones) stimulate the production or maintenance of proteins.  Catabolic hormones (e.g, glucocorticoids, thyroid hormone) stimulate the breakdown of proteins (18,19).

Cats Do Not Need Carbohydrate But Have High Protein Requirements

The cat, as a strict carnivore, has evolved to to depend on protein as a major energy source. The "natural" diet of cats in the wild is based upon the consumption of small mammals, birds, and insects — the composition of this diet is high in protein and fat but low in carbohydrate (20-22). This natural diet high in animal protein contains all of a cat's essential amino acids, which is not the case for plant-based proteins.

Cats have no dietary requirement or need for carbohydrate but are adapted physiologically and metabolically for high protein intake (23). In support of that, normal cats do well when fed diets containing 70% protein (24-27). The lack of a need for dietary carbohydrates is related to the fact that cats have developed a tremendous ability to synthesize their needed glucose from protein catabolism via hepatic gluconeogenesis (24,25,28).

Cats have a much higher protein requirement than other species, such as dogs and humans. The protein requirement for the adult cat is 2-3 times as much as the adult dog (23), and their protein requirement increases even further as cats reach old age (3,8-11). This high protein requirement of cats is primary related to the fact that cats have a limited ability to decrease the hepatic enzymes responsible for amino acid catabolism, even when fed a lower than optimal protein intake (24,29,30).

The Domestic Cat: A Metabolically Inflexible Carnivore

When most omnivores (e.g., humans, rats, pigs, dogs), ingest a diet high in protein, the activities of the amino acid-catabolizing enzymes in the liver increase to cope with the higher flux of amino acids (31-33). The activity of the urea cycle enzymes also increase to metabolize the increased ammonia generated upon the catabolism of the amino acids. On the other hand, when fed a diet low in protein, omnivores accommodate by lowering the hepatic activity of these catabolic enzymes of amino acid metabolism, as well as decreasing hepatic urea production (31-33).

By contrast, cats have a very limited ability to down-regulate these hepatic catabolic enzymes when fed a low-protein diet. In a classic study, Rogers et al (29) compared the activity of several catabolic enzymes of amino acid metabolism in adult cats fed either a high- or low-protein diet or fasted for 5 days. Results showed little changes in the hepatic enzyme activities between the 3 groups of cats, with hepatic enzyme activities remaining set at high levels to cope with a high protein diet (even when they weren’t being fed!).

Why would cats be so different?
Well, compared to other carnivores, cats may not be so strange after all. A similar degree of metabolic "inflexibility" has also been reported in other carnivores such as barn owls and the rainbow trout (34,35).

This limited metabolic flexibility in cats and other obligate carnivores likely represents an evolutionary adaptation to a consistently abundant supply of dietary protein. The moderately high and fixed activity of the urea cycle provides a safeguard against ammonia toxicity after ingestion of a high-protein meal. In addition, the high rate of amino acid catabolism allows for a readily available source of energy via direct oxidation or as a substrate for hepatic gluconeogenesis.

It is only when a cat is fed a lower protein diet, a condition that would never happen in the wild, that the high rate of protein catabolism becomes a disadvantage.

Bottom Line

• Unlike omnivores (dogs, pigs, rats, humans), cats have a limited ability to decrease the activity of the hepatic enzymes responsible for removing amino groups from the amino acids when fed a low protein diet. 
• Because these feline hepatic enzyme systems are constantly active, a fixed amount of dietary (or muscle) protein will always be catabolized for energy no matter how much energy in the form of carbohydrate or fat the cat ingests. 
• In addition, neither fat nor carbohydrates can be directly converted to amino acids to be made into protein. In this regard, the carnivorous cat is similar to omnivores.
• Overall, this explains why muscle wasting can occur so quickly in the older, geriatric cat, which becomes ill or develops a poor appetite or is fed a low-protein diet.

References:

1. Perez-Camargo G: Cat nutrition: What is new in the old? Compendium for Continuing Education for the Practicing Veterinarian 2004;26 (Suppl 2A):5-10.
2. Laflamme D. Nutrition for aging cats and dogs and the importance of body condition. Veterinary Clinics of North America: Small Animal Practice 2005;35:713-742.
3. Pérez-Camargo G. Feline decline in key physiological reserves: implication for mortality. Proceedings of the Nestlé Purina Companion Animal Nutrition Summit: Focus on Gerontology. St. Louis, MO. 2010, pp. 6-13.
4. Fujita S, Volpi E. Nutrition and sarcopenia of ageing. Nutrition Research Reviews 2004;17:69-76.
5. Paddon-Jones D, Short KR, Campbell WW, et al. Role of dietary protein in the sarcopenia of aging. The American Journal of Clinical Nutrition 2008;87:1562S-1566S. 
6. Short KR, Nair KS. Mechanisms of sarcopenia of aging. Journal of Endocrinological Investigation 1999;22(5 Suppl):95-105.
7. Wolfe RR. Sarcopenia of aging: Implications of the age-related loss of lean body mass. Proceedings of the Nestlé Purina Companion Animal Nutrition Summit: Focus on Gerontology. St. Louis, MO. 2010, pp. 12-17.
8. Little SE: Evaluation of the senior cat with weight loss, In: Little, S.E. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders, 2012;1176-1181.
9. Sparkes AH. Feeding old cats— An update on new nutritional therapies. Topics in Companion Animal Medicine 2011;26:37-42.
10. Patil AR, Cupp C, Pérez-Camargo G. Incidence of impaired nutrient digestibility in aging cats. Nestlé Purina Nutrition Forum Proceedings. 2003;26,2(A):72.
11. Wakshlag JJ. Dietary protein consumption in the healthy aging companion animal. Proceedings of the Nestlé Purina Companion Animal Nutrition Summit: Focus on Gerontology. St. Louis, MO. 2010, pp. 32-39.
12. Gross KL, Yamka RM, Khoo C, et al. Macronutrients. In: Hand MS, Thatcher CD, Remillard RL, Roudebush R, Novotny, BJ (eds), Small Animal Clinical Nutrition. Mark Morris Institute. 2010; 49-105. 
13. Davy KP, Horton T, Davy BM, et al. Regulation of macronutrient balance in healthy young and older men. International Journal of Obesity and Related Metabolic Disorders 2001;25:1497-1502.
14. Galgani J, Ravussin E. Energy metabolism, fuel selection and body weight regulation. International Journal of Obesity 2008;32 (Suppl 7):S109-119.  
15. Brody T. Nutritional Biochemistry. Second Edition. Academic Press. 1998.
16. New Oxford Dictionary of English. Oxford University Press, 2001.
17. Berg JM, Tymoczko JL, Stryer L. Protein turnover and amino acid catabolism. Biochemistry. 5th edition ed. New York: W H Freeman, 2002. 
18. Mitch WE. Mechanisms accelerating muscle atrophy in catabolic diseases. Transactions of the American Clinical and Climatological Association 2000;111:258-269. 
19. Riis AL, Jørgensen JO, Gjedde S, et al. Whole body and forearm substrate metabolism in hyperthyroidism: evidence of increased basal muscle protein breakdown. American Journal of Physiology: Endocrinology and Metabolism 2005; 288:E1067-1073. 
20. Myrcha A, Pinowski J. Weights, body composition and caloric value of post-juvenile molting European tree sparrows. Condor 1970;72:175–178.
21. Vondruska JF. The effect of a rat carcass diet on the urinary pH of the cat. Companion Animal Practice 1987;1:5-9.
22. Crissey SD, Slifka KA, Lintzenich BA. Whole body cholesterol, fat, and fatty acid concentrations of mice (Mus domesticus) used as a food source. Journal of Zoo and Wildlife Medicine 1999;30:222-227. 
23. National Research Council. Proteins and amino acids. In: Nutrient Requirements of Dogs and Cats. Washington, DC: National Academies Press. 2006; 111-145.
24. MacDonald ML, Rogers QR, Morris JG. Nutrition of the domestic cat, a mammalian carnivore. Annual Review of Nutrition 1984;4:521-562. 
25. Morris JG. Idiosyncratic nutrient requirements of cats appear to be diet-induced evolutionary adaptations. Nutrition Research Reviews 2002;15:153-168. 
26. Hendriks WH. Protein metabolism in the adult domestic cat (Felis catus). PhD Thesis, 1996. 
27. Hamper B, Bartges J, Kirk C, et al. The unique nutritional requirements of the cat: a strict carnivore In: Little SE, ed. The Cat: Clinical Medicine and Management. St. Louis: Elsevier Saunders, 2012;236-242.
28. Kettelhut IC, Foss MC, Migliorini RH. Glucose homeostasis in a carnivorous animal (cat) and in rats fed a high-protein diet. American Journal of Physiology 1980; 239:R437-440.
29. Rogers QR, Morris JG, Freedland RA. Lack of hepatic enzymatic adaptation to low and high levels of dietary protein in the adult cat. Enzyme 1977;22:348-356.
30. Green AS, Ramsey JJ, Villaverde C, et al. Cats are able to adapt protein oxidation to protein intake provided their requirement for dietary protein is met. The Journal of Nutrition 2008;1053-1060. 
31. Waterlow JC. The mysteries of nitrogen balance. Nutrition Research Reviews 1999;12:25-54. 
32. Rosebrough RW, Steele NC, McMurtry JP. Effect of protein level and supplemental lysine on growth and urea cycle enzyme activity in the pig. Growth 1983;47:348-260.
33. Schimke RT. Adaptive characteristics of urea cycle enzymes in the rat. Journal of Biological Chemistry  1962;237:459-68. 
34. Walton MJ. Metabolic effects of feeding a high protein/low carbohydrate diet as compared to a low protein/high carbohydrate diet to rainbow trout Salmo gairdneri. Fish Physiology and Biochemisty 1986;1;7-15. 
35. Meyers MR, Klasing KC. Low glucokinase activity and high rates of gluconeogenesis contribute to hyperglycemia in barn owls (Tyto alba) after a glucose challenge. Journal of Nutrition 1999; 129:1896-1904.  

Is It Feasible for Older Cats to Ingest the Optimal Amounts of Protein They Need Each Day?

As I discussed in my recent post on the “Optimal Protein Requirements for Older Cats and Cats with Hyperthyroidism,” the optimal daily protein intake for normal, young to middle-aged cats fed appears to be at least ~5.5 g/kg, whereas older cats and cats with hyperthyroidism need at least ~6.0-7.0 g/kg to prevent loss of muscle mass. If these cats already have loss of lean body mass (i.e., muscle wasting), they may require even higher amounts of daily protein to help restore lost muscle mass.

The major issue we face is to identify and feed a diet that will provide adequate amounts of protein to these older cats and cats with hyperthyroidism. Over the past couple of weeks, I’ve received a number of questions from veterinarians and concerned owners that I’d like to address. Here are the main ones:

• How do we calculate how much protein these foods actually provide?
• Is it even possible or practical to attempt to feed those amounts of protein?
• What if our cats won’t eat as much protein as we would like them to ingest?
• Why can’t we just increase the amounts of fat and carbohydrate fed to compensate for the senior (and hyperthyroid) cats’ increasing energy requirements?
• What about older cats that have chronic renal disease? Shouldn’t these cats all be on a low protein diet?

In this post, I plan to address the first three questions. I’ll follow-up with the last two questions in separate posts because of their importance in clinical practice.

How to Calculate the Protein Content of a Food: Dry Matter Basis vs. Metabolizable Energy

Cats in the wild typically ingest diets containing > 50% of these daily calories as protein (1-3), so that may be a good goal to shoot for when selecting the composition of a diet. When analyzing a diet, I like to examine or calculate the amount of the calories each nutrient (i.e., protein, fat or carbohydrates) provides — this is called the “metabolizable energy,” abbreviated ME (4,5). This measure disregards any part of the food that does not provide any energy (kcal) such as water, ash, or fiber. It only considers the 3 nutrients that provide the needed calories and nothing else.

Let’s take an example using 5 commercial foods containing a wide range of protein content. In each of these diets, I’ve set the fat content and calories (kcal) to be equal, but I’ve varied the protein and carbohydrate amounts. Remember, when we increase or decrease the levels of protein, we must always adjust the levels of carbohydrates, fat, or both to compensate. In other words, the percentage of calories that come protein, fat, and carbohydrates must equal 100% (% protein calories + % fat calories + % carbohydrate calories = 100% of the calories ingested).

So let’s take our first hypothetical diet, which on a dry matter (DM) basis contains 65% protein, 25% fat, and 4% carbohydrate (Table 1). To convert the nutrient composition from a DM to a ME basis, we must remember that protein and carbohydrate both provide approximately 3.5 kcal/g of food, whereas fat provides much more — approximately 8.5 kcal/g of food. Thus, in this diet, the energy provided by protein is 65% times 3.5 kcal/g, or 228 kcal, and the energy provided by fat and carbohydrate are 213 kcal and 14 kcal, respectively, for a total of 454 kcal. The percentage of metabolizable energy that is provided from protein is then calculated (by dividing 228 kcal by 454 kcal and multiplying by 100), which gives us a protein content (ME) of 50%.

Doing the same calculations for diets that contain protein levels (DM basis) of 55%, 45%, 35% and 30% are also included in Table 1. As you can see, looking at nutrients on a dry matter basis “overestimates” the calories provided by protein (ME basis) by ~30%, while greatly underestimating the calories provided by fat (by ~50% in this example).

Table 1. Comparison of Nutrient Content:
Dry Matter (DM) Basis vs. Metabolizable Energy (ME) Basis

Bottom Line: When analyzing the composition of a cat food, one can look at the protein content on a DM or ME basis. In the end, it doesn’t make that much of a difference, but one must realize that the percent protein on a DM basis “overestimates” the calories provided by protein (ME basis). Cats in the wild ingest at least 50% of their calories as protein (ME). As you can see, that equates to ~65% of their diet being composed of protein on a DM basis.

Calculating the Amount of Protein that Commercial Diets Provide

Once we select our diet, we can do the calculations for protein content of a can or cup of food, as I described in detail in my post on “Optimal Protein Requirements for Older Cats and Cats with Hyperthyroidism.” Again, for this calculation, we need to know the protein content of the diet (DM basis), as well as the moisture content of the diet (generally 75% for canned food and 10% for dry food diets).

Let’s take another example by examining 5 commercial foods containing a wide range of protein content (Table 2). All of these diets are 5.5 oz cans (156 g) containing 75% moisture, so this leaves us with 39 g of food in each can on a DM basis (156 times 25% = 39 g). From the information on the label or the company’s website, we will hopefully find the protein content (DM) of each diet (note that if the protein content on a DM basis is not listed, you will have to call the company for that information). The guaranteed analysis (GA) information cannot be used for this calculation, since it listed only the minimum percentage of the crude protein contained the product and is therefore highly inaccurate.

Once the protein content (DM) is know, we multiply that value by total dry matter weight of the can. This provides us with the total protein content in each can of food (e.g., 39 g times 65% = 25.4 g of protein).

In this example, I’ve then used the weight of an average older cat (4.5 kg) to calculate the amount of protein ingested on a body weight basis (g/kg).

Table 2: Calculation of Daily Protein Ingested Based on Protein Content of Food.
*Each 5.5 oz can contains 156 g of food. If moisture content of diet is 75%, that leaves 25% dry matter and 39 g of food (156 times 25% = 39 g).

Bottom Line: As you can see in Tables 1 & 2, we need to feed a diet containing at >50% protein (DM basis) or >40% protein on a ME basis to even come close to providing the needed amounts of protein per kg.

The pet food companies may tell you that these protein levels are unnecessary and that the Association of American Feed Control Officials (AAFCO) requires that feline diets contain a minimum of 26% DM protein for maintenance (4,6). But remember: those are “minimal,” not optimal values. And most importantly, those recommendations are for normal adult cats, not hyperthyroid cats or geriatric cats prone to muscle wasting associated with sarcopenia of aging (7,8).

Is It Even Possible to Feed the Optimal Amounts of Protein to these Geriatic Cats?

The average older cat weighs 10 lbs (4.5 kg); if our goal is to provide 6.0-7.0 g of protein/kg/day, that calculates into an optimal daily protein intake of ~27-31 g. To consume those amounts of protein, that 4.5 cat would have to eat almost three 5.5-oz cans of food per day containing 30% protein (DM), almost two cans of food per day containing 45% protein (DM), or just over one can of a food containing 65% protein (DM) (Table 2).

In general, older cats tend not to eat those large amounts of food each day, unless they have uncontrolled hyperthyroidism and are polyphagic (9,11). Most older euthyroid cats (again weighing 4.5 kg) would eat only one 5.5-oz can per day, which provides only ~2.6 g/kg/day to 5.6 g/kg/day (Table 2).

So what can we do to help prevent "sarcopenia of aging" with its associated muscle wasting in these older cats? We want to feed an energy dense food that contains a highly digestible, high-quality source of protein.

Feeding an Energy-Dense Diet to Older Cats & Cats with Hyperthyroidism

What if our cats won’t eat as much protein as we would like them to ingest?

1. In addition to providing a diet with an adequate amount of protein, we need to make sure that the cat’s energy requirement is fulfilled. Most of the cat foods marketed as “Senior” diets are too low in caloric content. Remember as cats age (>12 years), their energy requirements actually increase (8, 12-14); these cats will lose weight (and muscle mass) on many of these commercial senior diets.
2. When calorie intake is inadequate to meet energy needs, body proteins are catabolized and used for energy (4). Again, feeding frequent small meals of an energy-dense, highly digestible diet that meets the senior cat’s increasing energy requirements will minimize protein degradation and avoid protein:calorie malnutrition (8, 12-14).
3. Identify diets that are palatable for the cat. Many older cats may partially lose their sense of taste or smell. Feeding a variety of different flavors or types of food helps maintain the appetite in many of these older cats.
4. Warming the food to body temperature or moistening the food may increase help to increase appetite in some cats.
5. Feeding frequent small meals of energy-dense, fresh food may help increase daily food intake.
6. Cats are solitary feeders by nature and elderly cats often do not cope well with competition and stressors. Older cats in multi-cat homes may benefit from being fed separately or being offered supplemental meals.
7. One must also identify underlying medical problems that can lead to decrease in appetite (8,9).

Feeding Highly Digestible, High Quality Protein to Geriatric Cat & Cats with Hyperthyroidism

Again, how can we help compensate for the fact that many older cats will not eat enough food to fulfill their “optimal” daily protein needs? Again, the answer may lie in the source of the protein used in the cat food diet. Feeding a highly digestible, high-quality source of protein would likely allow us to feed lower amounts of protein but still prevent loss of lean body mass and muscle wasting. Improving protein quality without increasing protein intake may help fulfill of these additional protein needs of older cats (4,15).

It is generally accepted that animal protein has a higher digestibility and is of higher quality than that of plant protein sources (16,17). Proteins of plant origin usually have a lower digestibility than animal proteins because plant fiber and the carbohydrates found in plants lower digestion, due to a reduced degradation rate of nutrients in the gut and increased bacterial activity (18).

The biological value (or quality) of a protein is a measure of that protein's ability to supply amino acids (especially the 11 essential amino acids) and to supply these amino acids in the proper proportions (4,15,17). The higher the biological value of a protein, the less would be needed in the diet to meet all of an animal’s essential amino acid requirements.

Figure 1: Protein Biologic Value of Common Pet Food Ingredients. 
Data from reference no. 15.

As shown in Figure 1, it is well-established that animal proteins (e.g., meat, meat by-products) have a higher biological values than vegetable proteins (e.g., corn gluten meal, soybean meal, soy protein isolate) (15-17,19). To meet a cat’s optimal daily protein needs, less protein intake would be required when its biological value is high (e.g., when animal protein is fed as the main source of protein).

What About Hill’s y/d? Will Cats Really Eat the Recommended Amounts of y/d Diet Every Day for the Rest of Their Lives ?

Again, one must realize that the amount of protein a cat ingests per day is highly dependent upon the total amount of food consumed. Eating a diet with less-than-optimal quantities of protein might be adequate if that cat ingests a large enough quantity of the food.

The recommended amounts of y/d to feed, as listed on the Hill’s website (20,21), seem reasonable for an uncontrolled hyperthyroid cat. Once euthyroid, however, will the cats continue to consume those same amounts of food? No, that's highly unlikely.  In general, the amount of food hyperthyroid cats ingest decreases as euthyroidism is restored. But remember, older cats still need higher amounts of protein, even when not hyperthyroid, to maintain their muscle mass as they age.

Let’s again take our average older cat weighing 4.5 kg. For that cat to consume protein at our “optimal” amount of 6.0-7.0 g/kg/day, the cat would have to eat almost two 5.5-oz cans of canned Hill's y/d per day or ¾ cup of dry Hill’s y/d per day. Those amounts exceed the amounts listed on the Hill’s feeding guide (18,19). Again, most older euthyroid cats (again weighing 4.5 kg) would eat only one 5.5-oz can per day, which provides ~3.3 g/kg/day, about half of what they actually need.

What about the sources of protein for Hill's y/d diets? Do they include a high-quality, easily digestible source of protein? Are the ingredients of high biological value? Unfortunately, the answer to both questions is no —the ingredients present in y/d are far less than ideal for cats. In addition to the fact that y/d is a low-protein diet, much of the diet’s protein is derived from plant sources. This is especially true for the dry formulation, in which the only listed animal protein on the label is "dried egg product," and this is the fifth ingredient. In other words, this diet does not contain any meat. The primary protein source in dry y/d is corn gluten meal, commonly used in many pet foods because of its low cost.

For the canned formulation, the ingredients list is better in that the first 3 listed ingredients— liver, meat by-products, and chicken—all contain animal protein. Liver is a very nutritious organ meat and a good source of animal protein, but the daily feeding of a pet food containing liver as the first ingredient might be questioned. Do you want to feed your cats a liver diet at every meal for the rest of their lives? Would you consider that a healthy diet?

References

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5. Schenck PA. Nutrients. In: Home-Prepared Dog and Cat Diets.  Wiley-Blackwell. Ames IA, 2010; 23-49.
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9. The Special Needs of the Senior Cat. Information brochure, Cornell University College of Veterinary Medicine.   
10. Peterson ME, Kintzer PP, Cavanagh PG, et al. Feline hyperthyroidism: pretreatment clinical and laboratory evaluation of 131 cases. Journal of the American Veterinary Medical Association 1981;183:103-110. 
11. Broussard JD, Peterson ME, Fox PR. Changes in clinical and laboratory findings in cats with hyperthyroidism from 1983 to 1993. Journal of the American Veterinary Medical Association 1995;206:302-305. 
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15. Lewis LD, Morris ML, Hand MS. Nutrients. In: Small Animal Clinical Nutrition III. Mark Morris Associates. Topeka, 1987; 1-25.
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19. Feline Nutrition. http://maxshouse.com/feline_nutrition.htm
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21. Hill's Pet Nutrition website. Prescription Diet y/d Thyroid Feline Health (Canned).