Life Extension Magazine May 2003
Life Extension Animals Case Studies
It was five long days until the results came back. By then, Jack was barely hanging on. The report showed that Jack's kidneys were inflammed for no apparent reason. Little grains created by the immune system were filling up his kidneys, blocking the delicate filtering system. Something was needed that could counteract the inflammatory process. The vet decided that Jack needed an intensive program starting with N-acetylcysteine (NAC).
NAC is a form of the amino acid, cysteine, with multiple kidney-protective actions. The research on what NAC can do for the kidney (and the liver) is scientifically well-documented. In one recent study, researchers in Italy demonstrated that NAC normalizes creatinine levels in rodents with kidney failure. It reverses inflammation and restores filtration. Similar findings are reported by French researchers when NAC is given as a pretreatment before experimental kidney damage in rats. Without NAC, there is a 68% reduction in the ability of the kidneys to do their job. With it, the loss of kidney function is only 29%. A third study confirms that an infusion of NAC before and after experimental kidney damage doubles the kidney filtration rate. NAC is strong medicine for the kidneys. It has no adverse side effects, even when small animals like cats are given a human dose.
The veterinarian started Jack on 100 mg of NAC twice a day, plus a new diet of raw beef and chicken and 100 mg of DHEA (dehydroepiandrosterone). DHEA is critical for an important kidney enzyme known as sulfotransferase. People with kidney disease have depleted levels of DHEA. Research shows that DHEA and NAC probably work synergistically, which is why they were given together.
Within 24 hours of receiving NAC and DHEA, Jack began eating like a normal cat. He continued to vomit for several days (a side effect of kidney failure), but two weeks from the date of surgery, his BUN had dropped from 152mg/dl to 45.6mg/dl and he was up and around. At that point, the supplements were cut in half. A month later, Jack's blood tests were normal. That was over a year ago and Jack is still doing great. He is maintained on a high-protein diet along with 50 mg of NAC and 25 mg of DHEA a day.
Zoe, the hairless dog
Zoe was beginning to look more like a chihauhau than a Yorkshire terrier. The little dog belonging to Lynne and Frank Burger scratched at her back constantly, but nothing they did seemed to help. She was going bald. And not only that, she never wanted to play with her buddy, "Mr. Pug," anymore. She seemed to have nervous energy but no real energy. Smallest in a household of ten dogs, Zoe had a special treat added to her dry food: a "gourmet" food from the grocery store.
"Flea allergy" or "food allergy" is a common diagnosis for animals loosing their hair. It's a quick, eye-ball diagnosis rarely accompanied by laboratory tests. The cure is usually steroids plus one of the new pesticides that is put on the back of the animal and absorbed through the skin. The problem is that fleas are only one of many things that can cause hair loss, which is usually accompanied by some sort of skin disorder.
Researchers from Hungary recently reported that 17 dogs treated with pesticides, "restricted diets," steroids, antibiotics and other medications did not respond because they were infected with microorganisms that are not usually regarded as a problem. Yet when the bugs were eradicated with the proper drugs, the dogs got well. This points out the importance of finding the root cause of a persistent problem.
Another cause of hair loss is poor nutrition. There is considerable evidence that the nutritional requirements for dogs depends on the breed. It appears that dogs prone to certain disorders also require certain dietary needs. English setters, for example, can inherit a terrible disease called Batten disease which causes the brain to shrink. It is accompanied by abnormally low levels of polyunsaturated fatty acids and the amino acid, carnitine. Researchers at Indiana University wanted to see if it would help to supplement the animals diets' with carnitine, fish and corn oil. It did. Carnitine greatly reduced cognitive decline, and the combination reduced brain atrophy and extended lifespan 10%.
In 1988, veterinarians at the University of California at Davis reported on 13 dogs that had been eating a generic dry, corn and wheat-based dog food. The dogs were depressed and lethargic. They had swollen lymph nodes and, worst of all, they had scaly, crusting areas where their fur was falling out. The dog food the owners were feeding did not state that it met minimum nutritional requirements (AAFCO). When the animals were put on a higher-quality dog food, the animals began to get better within days.
Aging and dementia in dogs
Elderly dogs can act like elderly people who aren't quite "with it." The "not with it" part is caused by damage to brain cells-damage that accumulates over time. A small percentage of dogs can go on to develop an Alzheimer's-like condition. (Although under the microscope, doggie AD does not have all of the same features as human AD.) Symptoms of brain aging in dogs include sleep disorders, forgetting house-training, lethargy, disinterest, confusion about going in or out of doors, hiding and getting lost.
There are various supplements an owner can give their animals to protect them from degenerative diseases. DHEA (dehydroepiandrosterone), for example, is a hormone secreted by the adrenal glands that declines drastically with age. In a study from Purdue University, 100 mg/kg of DHEA a day given as a supplement for seven months to elderly dogs reduced the percentage of brain cells with extensive DNA damage by 42%. This shows that even an elderly animal can benefit from anti-aging interventions. In the same study, damage to the dogs' immune cells was cut in half. This is good health news for pet owners. Note that both types of cells (immune and brain) are extensively damaged in people with Alzheimer's disease. Its antioxidant action may account for DHEA's ability to protect these vital cells.
There are other methods to protect the brain as well. When the Science Diet® people went looking for a supplement that could help aging dogs stay alert, they focused on two important aspects of brain aging: energy and free radical damage.
The brain's energy is generated by sub-cellular structures called "mitochondria." When mitochondria make energy, free radicals are created. Free radicals, in turn, damage mitochondrial DNA. Damaged DNA, in turn, prevents the little power plants from producing energy efficiently. The vicious cycle is accelerated by age.
The brain is very susceptible to free radical damage because of its high fat content and high demand for energy. One of the most powerful brain antioxidants is alpha lipoic acid, also known as lipoic, or thioctic acid. Lipoic acid has multiple actions. On one level, it restores and maintains other antioxidants including vitamins C and E, and the natural antioxidant, glutathione, which is diminished in the brains of elderly dogs. Lipoic acid also enhances the level of coenzyme Q10, an energy-related enzyme, and restores arachidonic acid in brain cells to youthful levels. Arachidonic acid is absolutely critical for learning and remembering. Researchers have demonstrated that restoring arachidonic acid to youthful levels through supplements increases the ability of neurons to respond. In other words, arachidonic acid may be the key to teaching an old dog new tricks.
Additionally, lipoic acid can chelate iron and other metals, keeping them from fueling free radical chain reactions. By itself, lipoic acid is highly protective of brain cells, but there is another element that can be combined with it that makes it even more powerful: carnitine
Scientifically-proven anti-aging combination
Carnitine is an amino acid that has a special role in energy production. It transports fuel into mitochondria for conversion to energy-ATP. Carnitine levels decline with age, and so does its transport. By supplementing with carnitine, studies show that old mitochondria can have the energy production of young mitochondria. In a stunning report that was published in the Proceedings of the National Academy of Science, researchers at the University of California at Berkeley showed that elderly rats given L-carnitine doubled their activity to a level approaching that of young rats. (Young rats given L-carnitine were like five year-olds on jet fuel). Researchers were able to correlate increased activity with increased energy production in the animals' mitochondria.
As great as it was to get the old mice up and going again, their increased energy came with a price: a 30% increase in free radicals. This is where lipoic acid comes into the picture. When the same researchers added lipoic acid to the L-carnitine supplements, oxidative stress was reduced to the level of youngsters and physical activity was even greater than that achieved with lipoic acid alone. Memory was enhanced, and when the researchers looked at the hippocampus-a brain structure having to do with memory-they found that the combination of L-carnitine and lipoic acid actually kept the mitochondria from aging.
For years nobody paid much attention to the diets of their cats and dogs. They got the scraps off the table, or the mice from the barn and that was about it. But when these animals began being used in laboratories, it became imperative to know their nutritional requirements. "Complete and balanced nutrition" pet food is a billion dollar offshoot of "lab chows." The industry has contributed substantially to understanding the nutritional requirements of our "best friends." But science is moving on now, beyond what it takes to keep an animal on its feet, to what it takes to keep an animal healthy in the long run. New research shows that cats and dogs respond positively to some of the same supplements we take. Lower vet bills and happier animals is our reward for optimal nutrition.
To view which brands of dog food contained detectable levels of pentobarbital in the FDA study, see http://www.fda.gov/cvm/efoi/DFchart.pdf. For a brief report of the study, see http://www.fda.gov/cvm.
Earth Island Institute has done several reports on commercial pet food and rendering plants, including "The Dark Side of Recycling", fall 1990; "Food Not Fit for A Pet", summer 1996. "Look Inside" a Rendering Plant, summer 1996. See www.earthisland.org.
Cats are strict carnivores. Their requirement for meat protein is three times higher than omnivores like dogs. They must have meat protein to maintain health. Meat should be the first ingredient in a cat's diet. Commercial pet food made with human-grade meat is available online. Brands include Wysong, Wellness, PetGuard and Active Life.
Ann Martin looked into the pet food industry after her own dog almost died from contaminated commercial dog food. An updated version of her book, Food Pets Die For is now available for $13.95. Call, toll-free, 877-695-2211 or visit www.newsagepress.com. The book is also available through bookstores online.
Martin Goldstein is a Cornell-educated veterinarian who practices holistic vet care. The Nature of Animal Healing. (Knopf 1999).
Mazzon E, et al. Effect of N-acetylcysteine on gentamicin-mediated nephropathy in rats. Eur J Pharm 2001, 424:75-83.
Conesa EL, et al. N-acetylcysteine improves renal medullary hypoperfusion in acute renal failure. Am J Physiol Regul Integr Comp Physiol 2001, 281:R730-7.
DiMari J, et al. N-acetylcysteine ameliorates ischemic renal failure. Am J Physiol 1997, 272(3 Pt 2):F292-8.
Parker CR, et al. The localization of DHEA sulfotransferase in steroidogenic and steroid metabolizing tissues of the adult rhesus macaque monkey. Endocr Res 2000, 26:517-22.
Cameron NE, et al. Effect of alpha-lipoic acid on vascular responses and nociception in diabetic rats. Free Radic Biol Med 2001, 31:125-35.
Packer L, et al. Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radic Biol Med 1997, 22:359-78.
Gotz ME, et al. Effect of lipoic acid on redox state of coenzyme Q in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and diethyldithiocarbamate. Eur J Pharmacol 1994, 266:291-300.
Muller U, et al. Prolonged pretreatment with alpha-lipoic acid protects cultured neurons against hypoxic, glutamate-, or iron-induced injury. J Cereb Blood Flow Metab 1995, 15:624-30.
Barbiroli B, et al. Lipoic (thioctic) acid increases brain energy availability and skeletal muscle performance as shown by in vivo 31P-MRS in a patient with mitochondrial cytopathy. J Neurol 1995, 242:472-7.
McGahon BM, et al. Age-related changes in LTP and antioxidant defenses are reversed by an alpha-lipoic acid-enriched diet. Neurobiol Aging 1999, 20:655-64.
Hagen TM, et al. Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proc Natl Acad Sci 1998, 95:9562-66.
Hagen TM, et al. Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci 2002, 99:1870-5.
Liu J, et al. Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetylcarnitine and/or R-alpha-lipoic acid. Proc Natl Acad Sci 2002, 99:1876-81.
Liu J, et al. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetylcarnitine and /or R-alpha-lipoic acid. Proc Natl Acad Sci 2002, 99:2356-61.
Head E, et al. Oxidative damage increases with age in a canine model of human brain aging. J Neurochem 2002, 82:375-81.
Hounsom L, et al. Oxidative stress participates in the breakdown of neuronal phenotype in experimental diabetic neuropathy. Diabetologia 2001, 44:424-8.
McGahon BM, et al. Age-related changes in LTP and antioxidant defenses are reversed by an alpha-lipoic acid-enriched diet. Neurobiol Aging 1999, 20:655-64.
McGahon BM, et al. Age-related changes in synaptic function: analysis of the effects of dietary supplementation with omega-3 fatty acids. Neuroscience 1999, 94:305-14.
Ramakers GM, et al. A postsynaptic transient K(+) current modulated by arachidonic acid regulates synaptic integration and threshold for LTP induction in hippocampal pyramidal cells. Proc Natl Acad Sci 2002, 99:10144-49.
Ford I, et al. The effects of treatment with alpha-lipoic acid or evening primrose oil on vascular hemostatic and lipid risk factors, blood flow and peripheral nerve conduction in the streptozotocin-diabetic rat. Metabolism 2001, 50:868-75.
Greene EL, et al. Alpha-lipoic acid prevents the development of glucose-induced insulin resistance in 3T3-L1 adipocytes and accelerates the decline in immunoreactive insulin during cell incubation. Metabolism 2001, 50:1063-69.
Yorek MA, et al. Effect of increased concentration of D-glucose or L-fucose on monocyte adhesion to endothelial cell monolayers and activation of nuclear factor-kappaB. Metabolism 2002, 51:225-34.
Tarello W. Dermatitis associated with Dirofilaria (Nochtiella) repens microfilariae in dogs from central Italy. Acta Vet Hung 2002, 50:63-78.
Siakotos AN, et al. Assessment of dietary therapies in a canine model of Batten disease. Eur J Paediatr Neurol 2001, 5 Suppl A:151-6.
Sousa CA, et al. Dermatosis associated with feeding generic dog food: 13 cases (1981-1982). JAVMA 1988, 192:676-80.
Morris JG, et al. Assessment of the nutritional adequacy of pet foods through the life cycle. J Nutr 1994, 124:2520S-34.
Czarnecki-Maulden GL, et al. Evaluation of practical dry dog foods suitable for all life stages. JAVMA 1989, 195:583-90.
Kittleson MD, et al. Results of the multicenter spaniel trial (MUST): taurine- and carnitine-responsive dilated cardiomyopathy in American cocker spaniels with decreased plasma taurine concentration. J Vet Intern Med 1997, 11:204-11.
Maia OB, et al. Evaluation of the components of a commercial probiotic in gnotobiotic mice experimentally challenged with Salmonella enterica subsp enterica ser Typhimurium. Vet Microbiol 2001, 79:183-9.
Chew BP, et al. Dietary ß-carotene absorption by blood plasma and leukocytes in domestic cats. J Nutr 2000, 130:2322-25.