19.2.07

Herbal Ingredients

Alfalfa
At first, although there were rumblings about the toxicity of alfalfa on such websites as the ASPCA, there was little substance to sustain the comments I was reading. Eventually, with a little work, here is some of what surfaced:

Alfalfa may, because of the presence of eugenol in the herb, inhibit certain liver microsomal hydroxylating systems. This produces toxic effects from drugs normally metabolized by those systems.

Among the several phenolic compounds assayed for their phytotoxicity on root and shoot growth of alfalfa, coumarin and trans-cinnamic acid at 60 +/- 10 micrograms mL-1 were the most inhibitory. Mixtures of five or more phenolic acids were more phytotoxic than their respective individual components except in the case of trans-cinnamic acid and coumarin.

Alfalfa = Coumarin (acts as an anticoagulant)

Warfarin toxicity can occur as a result of ingestion of pharmaceutic Coumadin or after exposure to the rodenticide superwarfarins. It may be from intentional or unintentional overdose or as a consequence of drug interactions.

The story of the anticoagulant-cum–rat poison begins with an agricultural strategy of the early 1900s, the introduction of sweet clovers in the North American prairies. In 1924 ranchers in Alberta, Canada, observed that cattle feeding on moldy sweet clover were dying from a hemorrhagic disorder; the active agent was found to be dihydroxycoumarin (coumarin itself is shown below). This molecule was synthesized within a year and quickly found use as an anticoagulant. Meanwhile warfarin, the derivative of coumarin, was developed by University of Wisconsin biochemists Mark A. Stahmann and Karl P. Link, and used as a rodenticide. It took 10 years for it to enter clinical practice as a blood-thinner.

Aloe

Aloe is a member of the lily family, and there a number of varieties, some more of a problem than others. There are more than 500 species of aloe growing in a variety of climates worldwide and only three or four of those are reported to have medicinal properties. Sabaea is particularly bad with compounds such as coniine, which is capable of producing both depressant and excitatory effects on the spinal cord of the cat. It has been compared with curare, and strychnine. This type of information is important if you are growing aloe plants in your house, and possibly applying aloe externally for skin irritations and other folk remedies, as there needs to be specific processing done on a safe variety in order for the resulting product to be "food grade" for your cat, as your cat licks his or her fur.

The variety barbadensis has been known to cause hepatitis in humans on a number of occasions.

Depending upon the variety of aloe, and the processing done, to prepare it, there are a number of ways it is used as a human medicine, such as as a laxative and skin salve, a cancer treatment, a glucose control mechanism, and immune system enhancer, however, if you have any plans to use this plant on your cat, or internally, I would definitely look into the variety source and chemicals used for processing further, based upon the chemicals this plant contains that are harmful. Keep in mind the term "Food Grade" when searching for a suitable source. There are also warnings out there that aloe compounds can interfere with regular medications, causing them to be less effective, at best.

Chlorophyll

Here is an ingredient you wouldn't expect to see on this list, however, if your pet is prone to struvite crystals, be aware that chlorophyll contains magnesium as the core of its molecule, and magnesium is said to contribute to struvite crystals in cats.

Rosemary
Essential oils of rosemary have demonstrated antimicrobial, hyperglycemic, and insulin-inhibiting properties.98,99 The next site states: "These data suggest that the volatile oil of R. officinalis has hyperglycemic and insulin release inhibitory effects in the rabbit."

A postprandial elevation in plasma glucose levels 30 min after administration of maltose or sucrose plus the distilled extract was significantly suppressed compared with glucose levels in mice that did not receive the distilled extract.

Garlic and Onion

In particular Onion, more than garlic, is a blood thinner, and doesn't go well with home testing where you may need your cat's blood to clot within a reasonable time. In fact, my own experience with this was when Hamlet had been sunning himself on the deck, next to the chives, on a day when I was doing a curve. It wasn't until the second time that I smelled freshly chopped chives and realized that the copious amount of blood that came with the small prick of the lancet was a result of Hamlet cheating with the chives. They contain Sodium 2-Propenyl Thiosulfate that oxidizes, (rusts), erythrocytes, also known as red blood cells which is where the term anemia evolves in the well known condition, Hemolytic anemia. Propylene Glycol, sometimes found in pet foods, causes the same effect.

Yucca schidigera
Yucca schidigera extract is included in pet foods to reduce faecal aroma, as an aesthetically pleasing ingredient for humans, rather than a nutritional additive for felines. What pet owners are not told is that the results of the study mentioning the motivation, above, also states the following: " Blood urea increased significantly in YSE-treated cats, possibly due to the saponins of YSE affecting gut wall permeability. This finding contrasts with previously published reports of a reduction in blood urea on the addition of sarsaponin (from YSE) to rat diets and of YSE products to poultry and cattle diets." In other words, while yucca is not showing harmful side effects in studies on other animals, and chickens, cats, with their more sensitive GIT DOES show an effect in lab results for cats.As stated in the British Journal of Nutrition, Volume 88, Number 6, December 2002, pp. 587-605(19), "These structurally diverse compounds have also been observed to kill protozoans and molluscs, to be antioxidants, to impair the digestion of protein and the uptake of vitamins and minerals in the gut, to cause hypoglycaemia, and to act as anti fungal and antiviral agents. These compounds can thus affect animals in a host of different ways both positive and negative."Yucca is also a member of the Liliaceae family. The University of Pennsylvania suggests that members of the lily family have long term effects, "consistent with acute renal failure".

Vegetables and Fruits

Fruits and vegetables contain glutamic acid, which cats have a lower tolerance for than other species. The explanation in Comparative Nutrition of Cats and Dogs, Annu. Rev. Nutr. 1991. 11.’239~5, as an example, is that it is "probably due to the low activity of alanine aminotransferase in gut mucosa of cats", quoted from Rogers, O.R., Phang, J.M. 1985. Deficiency of pyrroline-5-carboxylate synthase in the intestinal mucosa of the cat. J. Nutr. 115:146-50

Avocado

The information around avocado use is usually a little ambiguous which may help to explain why avocado is promoted in one particular pet food, however, it is not something I personally would feed my cats, based upon the following:

"Avocados contain a toxic component called persin," explains Jill A. Richardson, DVM, of the ASPCA Animal Poison Control Center (APCC), "which has been shown to produce cardiac tissue damage, respiratory distress and mammary gland damage in a variety of animals--including horses, goats, sheep, dogs, cattle, rabbits, fish and birds."

The above information is repeated frequently on the net if you do a search.

Etiology:
Ingestion of fruit, leaves, stems, and seeds of avocado has been associated with toxicosis in animals; leaves are the most toxic part. The Guatemalan varieties of avocado have been most commonly associated with toxicosis

If I had a cat that required tamoxifen I might feel comfortable adding avocado to the diet as Persin is supposed to compliment the chemotherapy action of this drug, however, I would never let avocado near a cat with a heart weakness:

Clinical signs: vomiting, diarrhea, death, inflammation of mammary glands of rabbits, goats, cattle, and horses- Cardiac failure in goats- Respiratory distress, generalized congestion, fluid accumulation around the heart.

In Ramesh Gupta's "Veterinary Toxicology, Basic and Clinical Principles" (2007), avocado is listed under Table 13.1, 'Plants affecting the heart', in reference to cardiac glycosides on page 196:
"Interefere with the Na+/K+-ATPase enzyme in cardiac fiberes resulting in decreased intracellular K+ and increased intracellular Na+ causing various degrees of heart block" This section was written by Steven I Baskin, Steven E Czerwinski, Jaime B. Anderson, and Manu M. Sebastian and, as I prefer to see, had reputable references sources for their comments including Akera et al (1973), for those who wish to dig further.

There are warnings regarding human consumption of avocado fruit:

These data suggest that consumption of avocado oil extracted from intact fruit may cause changes in liver metabolism.

Avocado Interactions
Avocado ingestion may decrease the anticoagulant effect of warfarin. Patients taking warfarin should consult their health care provider before eating avocado or taking herbal products.
Avocado Adverse Reactions
Allergy to latex, bananas, melons, and peaches may result in a cross-sensitivity to avocado; if allergic, use products that contain avocado with caution.

Cranberries

The cranberry industry is targeting pet foods as a source of income, with no concern for the effect of benzoic acid, or other issues involved that affect felines. Even in the attached Wikipedia site they mention, "Cats have a significantly lower tolerance against benzoic acid and its salts than rats and mice".

Benzoic acid toxicity in felines is well documented online at sites such as the following:
Outbreaks of poisoning affecting 28 cats have followed ingestion of meat containing 2.39% benzoic acid. The effects were nervousness, excitability, and loss of balance and vision. Convulsions occurred and 17 cats either died or were killed. Autopsies showed damage to intestinal mucosa and liver. The sensitivity of the cat may be due to its failure to form benzoyl glucuronide and toxicity may develop with quantities greater than 0.45 g/kg single doses or 0.2 g/kg repeated doses (Bedford & Clarke, 1971).

In cats, glucuronidation is generally very low (Williams, 1967).

CHEMINFO Record Number: 374, states, "Ingestion:
Convulsions and death were observed following single oral doses of greater than 450 mg/kg benzoic acid to cats. Similar effects were observed following daily doses of greater than 200 mg/kg. The authors conclude that these effects are likely specific to cats.(12) "

Cranberries are sometimes recommended for reduction of crystal growth, but there have been studies showing that cranberries are not effective for this. As the first study here shows that it is the benzoic acid that is supposed to suppress crystals, this is not a healthy option for cats.

Cranberries also contain Salicylic acid that is very similar to aspirin. Aspirin is not good for pets.

Apples
Contain various sugars, and phenols that are not appropriate for felines. If your cat has allergies to pollen, you may find apples affecting this condition. Apples also contain Oxalic acid 500 µg that will contribute to crystal formation. Apple fibre also lowers the digestibility of proteins. Apples also contain phenols that are known to be irritants specifically to cats, (well known in cleaning products), and may cause dermatological discomfort at the least. If the seeds are included in the content included in a food, then amygdalin has been known "in rare cases to be fatal."

Potatoes
The Cornell Book of Cats 2nd edition, p. 383, Reference Guide: First Aid for Plant Poisoning states the following about the green peel on potatoes:
"Type of Illness: Lower Gastrointestinal
Vomiting, abdominal pain, bloody diarrhea, dry mouth, all after a latent period of 18-24 hours after plant was eaten. May proceed to nervous system stimulation followed by, i.e., trembling, salivation, and paralysis. May lead to cardiac arrest."

Cornell clarifies that the part of the plant they are describing are, "Nightshades, Jerusalem cherry, Potato (green parts and eyes)." While we should be able to have confidence in the term "human grade", it is very easy to see green parts on potatoes in supermarkets that humans are expected to prepare by removing the peal. I don't see that happening with pet foods, however, that is my personal opinion. The glycoalkaloids are also in bruised potatoes and flesh irritated by micro-organisms.

Then there are other sites online that you may access, such as here, and here, with the second site stating that these alkaloids are not removed with cooking.

Tomatoes
Along with the site above you can access Cornell who include the "solanum-type glycoalkaloids" as part of their poison plant section. Lower on the same page, after clarifying that it is the greener tomatoes that will be a risk, they echo the fact, "These alkaloids are not destroyed by cooking or drying at high temperatures" Tomato Puree contains 16.4 grams of carbohydrate per 100 grams of tomato.

Preservative Chemicals

BHA
Thompson D, Moldeus P, Biochem Pharmacol 1988 Jun 1;37(11):2201-7
"...Using isolated rat liver mitochondria we observed that both BHA and BHT inhibited respiratory control primarily by stimulating state 4 respiration and thus acting as membrane uncouplers. BHA and BHT also effectively dissipated membrane potential across the mitochondrial membrane and caused the release of calcium and mitochondrial swelling. These mitochondrial effects were reflected by a rapid decrease in ATP levels in intact hepatocytes which preceded cell death...."
Takami M, Preston SL, Toyloy VA, Behrman HR., The American Journal of Physiology 1999 Apr;276(4 Pt 1):E684-8
Reproductive Biology Section. . . Yale University School of Medicine
" We previously showed that the cell-permeant antioxidant 2(3)-tert-butyl-4-hydroxyanisole (BHA) inhibited germinal vesicle breakdown (GVBD) in oocyte (egg)-cumulus complexes (OCC) of the rat. . . . Spontaneous GVBD in OCC incubated for 2 h was significantly inhibited . . .by . . . NDGA . . . BHA . . . octyl gallate . . . ethoxyquin . . . . . . BHT . . . Antioxidants that had no effect on oocyte maturation at the same concentration . . . included ascorbic acid, vitamin E, and Trolox. . . . Oocyte maturation was induced by incubation of follicles for 3 h with human chorionic gonadotropin (hCG), and this response was inhibited by BHA or NDGA. These findings support the conclusion that cell-permeant antioxidants inhibit spontaneous resumption of meiosis (special cell division for eggs or sperms), which may implicate a role of oxygen radicals in oocyte maturation"
However, BHA induces in animals tumours of the forestomach, which are dose dependent, wherease BHT induces liver tumours in long-term experiments.
Zoccarato F, Pandolfo M, Deana R, Alexandre A, Biochem Biophys Res Commun 1987 Jul 31;146(2):603-10
"...While the Ca2+ uptake observed under non depolarizing conditions is not affected by these agents, the depolarization induced Ca2+ uptake is strongly inhibited. ..."
Stokes JD, Scudder CL, Dev Psychobiol 1974 Jul;7(4):343-50
"The chronic ingestion of .5% butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) by pregnant mice and their offspring resulted in a variety of behavioral changes. Compared to controls, BHA-treated offspring showed increased exploration, decreased sleeping, decreased self-grooming, slower learning, and a decreased orientation reflex. BHT-treated offspring showed decreased sleeping, increased social and isolation-induced aggression, and a severe deficit in learning." Cited here.
Stolze K, Nohl H., Free Radical Research 1999 Apr;30(4):295-303
" . . . tBHQ significantly increased the amount of high molecular weight degradation products of erythrocyte membrane constituents. These changes were only observed when incubations were performed in the presence of oxygen. . . These observations can be interpreted in terms of metabolic activation of the antioxidant BHA via tBHQ . . . thereby leading to harmful effects on erythrocyte (red blood cell) membrane structures. Moreover, deleterious effects on other biological membranes are also likely to occur. "
Vorhees CV, Butcher RE, Brunner RL, Wootten V, Sobotka TJ, Neurobehav Toxicol Teratol 1981 Fall;3(3):321-9
"Comparison of the present results to a similar study using BHT clearly indicates that BHA at equivalent dietary doses is considerably less toxic than BHT. The present results also suggest that BHA is not a potent behavioral toxin, although it is developmentally toxic using non-behavioral measures."
Sarafian TA, Kouyoumjian S, Tashkin D, Roth MD, Toxicol Lett 2002 Jul 21;133(2-3):171-9
" ... BHA alone, at concentrations of 10-200 microM, produced limited cell toxicity but significantly enhanced the necrotic death resulting from concurrent exposure to THC. ... The combination was synergistic in this respect, reducing ATP levels to <15%>
BHT:
Tryphonas H, Lacroix F, Lok E, Jee P, Clayson DB, Hayward S, Miller D, Mehta R, Food Chem Toxicol 1999 Jul;37(7):671-81
"...The induction of EAF and/or 0.5% BHT treatment resulted in a significant reduction in the natural killer (NK) cell activity of splenocytes...."
Osmundsen PE, Contact Dermatitis 1980 Dec;6(7):452-4
"...In one of the patients contact with plastic articles also provoked urticaria. A 20-min patch test with several articles of plastic (polyethylene and PVC) and with butylhydroxytoluene (BHT) 1% in ethanol elicited urticarial reactions. BHT is used as an antioxidant in plastic..."
Siman CM, Eriksson UJ, Toxicol Lett 1996 Oct;87(2-3):103-8
"The results show that BHT has adverse effects in the liver. BHT is metabolized by the cytochrome P450 system in the liver and may be converted to prooxidative compounds during this process. "
McFarlane M, et al., Food Chem Toxicol 1997 Aug;35(8):753-67
"...Dams [mother rats] receiving BHT at a nominal dose of 500 mg/kg body weight/day showed liver enlargement accompained by induction of pentoxyresorufin O-depentylase and glutathione S-transferase, and proliferation of the endoplasmic reticulum. Pups from these dams were of the same weight at birth as controls but lost weight during the lactation period. This deficit was not recovered by the time the experiment was terminated. ..."
Umemura T, Kodama Y, Hioki K, Nomura T, Nishikawa A, Hirose M, Kurokawa Y. Jpn J Cancer Res. 2002 Aug;93(8):861-6.
" We have demonstrated the utility of a 9-week in vivo two-stage assay for lung cancer initiating agents, using transgenic mice ...and butylhydroxytoluene (BHT) as a potent lung promoter .... Additionally, use of BHT was validated for promotion of urethane (UR) carcinogenesis in male and female rasH2 mice.... In a dose-response study, effects were dose-dependent, the dose of 400 mg/kg causing eight-fold elevation as compared to the control.... "
Malkinson, AM, Crisp Data Base National Institutes Of Health 1999
"...The food additive, butylated hydroxytoluene (BHT), encourages the development of tumors from previously initiated cells. ...Chronic administration of BHT to inbred mice down-regulates the pulmonary concentrations of the alpha isozyme of protein kinase C (PKCa) and calpain in promotion-sensitive strains ... " The researchers are searching for the gene responsible.
Kovaleva ES, Prilipko LL, Muranov KO, Kagan VE, Biull Eksp Biol Med 1983 Oct;96(10):55-7
"..All free radical scavengers used inhibited 3T-hydroxytryptamine uptake and stimulated 3H-hydroxytryptamine release, with the efficacy being reduced in the following order: 7-hydroxyaminazine greater than butylated hydroxytoluene greater than paginol-2-methyl-6-ethyl-3-hydroxypyridine greater than alpha-tocopherol..."
Tanaka T, Oishi S, Takahashi O. Toxicology Letters 1993 Mar;66(3):295-304
" Butylated hydroxytoluene (BHT) was administered to mice, . . . in the diet at levels of 0 (control), 0.015, 0.045, 0.135, and 0.405%, . . . .The body weight of the pups of the 0.015% BHT group was increased at birth and during the lactation period for each generation. . . In the neurobehavioural parameters, a few parameters were increased in treatment groups; i.e., surface righting . . . and negative geotaxis . . . "
Meyer O, Hansen E, Toxicology 1980;16(3):247-58
"...The applied dose of BHT [500 mg/kg to rats] exerted a significant adverse effect on body weight in both F0 and F1-animals and on several developmental parameters in F1-animals. The effects arose during the lactation period."
Safer AM, al-Nughamish AJ, Histol Histopathol 1999 Apr;14(2):391-406
"BHT resulted in a significant increase in liver weight. The liver cells presented gradual vacuolization, cytoplasmic disintegration, "moth-eaten" appearance, ballooning degeneration, hepatocellular necrosis, aggregation of chromatin material around the periphery of the nuclear envelope, SER proliferation, RER clumping with broken cisternae, withered and autolyzed mitochondria, augmentation of lipid droplets and glycogen depletion. "
Ohno Y, Takuma T, Asahi K, Isono K, FEBS Lett 1984 Jan 9;165(2):277-9
"Butylated hydroxytoluene (BHT) ... has been found to induce the differentiation of murine erythroleukemia cells. BHT also amplifies the differentiation inducing activity of DMSO."
Faine LA, Rodrigues HG, Galhardi CM, Ebaid GM, Diniz YS, Fernandes AA, Novelli EL. Exp Toxicol Pathol. 2006 Jan;57(3):221-6. Epub 2005 Dec 9
"The heart of BHT animals showed alteration of antioxidant defenses and increased concentrations of lipid hydroperoxides, indicating elevated lipoperoxidation. TG concentrations and lactate dehydrogenase activities were elevated in the cardiac muscle of BHT animals. Thus, long-term administration of BHT is capable to induce oxidative and metabolic alterations similarly to some pathological disorders, constituting an efficient experimental model to health scientific research."

Ethoxyquin:
Blaszczyk A, Toxicol Lett. 2006 May 5;163(1):77-83. Epub 2005 Nov 2
"This compound was recently found to cause not only many unfavourable side-effects in animals fed with feeds containing it, but also adverse effects in people exposed to it at work. "
Blaszczyk A, Skolimowski J. Acta Pol Pharm. 2005 Mar-Apr;62(2):111-5
"It was shown that EQ induced apoptosis in cultured human lymphocytes, especially at 0.25 and 0.5 mM concentrations."
Blaszczyk A, Osiecka R, Skolimowski J. Mutat Res. 2003 Dec 9;542(1-2):117-28.
"The results of the chromosome aberration assay showed that EQ induces chromosome aberrations: gaps and breaks as well as dicentrics and atypical translocation chromosomes."
FDA:
"However, after recently completing a scientific review of a voluntarily-submitted study from the Monsanto company, CVM has reason to believe that the 150 ppm level may not provide an adequate margin of safety in lactating female dogs and possibly puppies. The results from this study show that ethoxyquin levels above the current tolerance in dog foods produced no adverse reproductive effects. There was, however, an increase in a dark, reddish-brown pigment in the liver of female dogs immediately after completing a 6-week lactation. The liver pigment was identified as protoporphyrin IX, a normal intermediate in the synthesis of heme. This pigment was also associated with elevations in liver-related enzymes in the serum of a few animals. "
MSDS Sheet:
"May be harmful by ingestion, inhalation and through skin contact."
CBC:
"Ethoxyquin was originally developed as a rubber stabilizer. The Monsanto corporation later refined it for use as a preservative in animal feeds. Most dog foods contained very little of the chemical. But in the late 1980s, many companies that were making high performance foods began adding extra ethoxyquin. The foods contain more fat than regular dog foods, and the companies found the chemical to be a cheaper, more effective way to extend the shelf-life of their product. Not long after, some breeders were finding their dogs were developing unusual disorders."

Propyl Gallate:
D. Muñoz, M. Audicana, G. Gastaminza and E. Fernández. Allergology and Clinical Immunology Service, “Santiago Apóstol” Hospital, Vitoria-Gasteiz, Spain Contact dermatitis due to gallates
"Gallates are antioxidant compounds that are used in the food, cosmetics and
drug industries. Even though they behave as powerful antigens in animal models,
only a rather limited number of cases of gallate-induced contact dermatitides
has been reported in humans. This phenomenon has been attributed to immunologic
tolerance through oral exposure, as described in experimental animal
models."
Kraus AL, Stotts J, Altringer LA, Allgood GS, Procter and gamble Company, Cincinnati, Ohio 45241.
"The antioxidant propyl gallate, in a deodorant product, caused an allergic contact dermatitis in 1 subject during developmental controlled use testing. Subsequent dose response elicitation studies with this subject revealed a differing threshold of sensitivity to propyl gallate dependent upon application method."
Bojs G, Nicklasson B, Svensson A, Contact Dermatitis 1987 Nov;17(5):294-8
"The antioxidant propyl gallate in a moisturizing cream caused an allergic contact dermatitis in a patient previously sensitized to gallates while working in a bakery."
Hausen BM, Beyer W, Contact Dermatitis 1992 Apr;26(4):253-8
"A literature review revealed that the frequency of reports of allergic contact dermatitis from antioxidants of the gallate type has increased in the last 4 years. In most cases, the moderate sensitizer propyl gallate was the source of sensitization."

Sodium Benzoate: See Benzoic Acid toxicity under "Cranberries" above.

tBHQ:
Peters MM, Rivera MI, Jones TW, Monks TJ, Lau SS.
" 3-tert-Butyl-4-hydroxyanisole and tert-butyl-hydroquinone (TBHQ) are antioxidants known to promote renal and bladder carcinogenesis [cancer] in the rat, although the mechanisms of these effects are unclear....Because some chemicals may induce carcinogenesis by a mechanism involving cytotoxicity followed by sustained regenerative hyperplasia, our results suggest that the toxicity of GSH conjugates of TBHQ to kidney and bladder may contribute to the promoting effect of 3-tert-butyl-4-hydroxyanisole and TBHQ in these tissues. "
Patrick E, Juberg DR, O'Donoghue J, Maibach HI. Food Chem Toxicol 1999 Feb-Mar;37(2-3):169-75
" tert-Butyl hydroquinone (TBHQ) has important and functional uses in consumer and commercial applications, some of which involve human exposure primarily through dermal (skin) contact. . . . . Repetitive exposure to concentrations of 1.0% and 5.0% TBHQ and HQ were slightly to moderately irritating, while 0.1% of each of these test materials produced only weak irritant responses. . . . this study showed that TBHQ causes depigmentation in black guinea pigs at concentrations of 1% or greater. . . "