How Your Old Dog
Can Learn New Tricks

Dietary Supplementation with MCTs Has Long-Lasting
Cognition-Enhancing Effects in Aged Dogs

By Durk Pearson & Sandy Shaw®

A

very interesting new paper1 reports that supplementation with medium-chain triglycerides (MCTs) in aged beagle dogs resulted in significantly better cognitive performance in most of the different test protocols than the aged control beagle dogs and, most interestingly, performance of the more difficult tasks showed greater effects of supplementation than that of the easier tasks.

The authors were motivated to do their trial by research investigating the declines in cerebral glucose metabolism that start around middle age and contribute importantly to cognitive decline associated with aging and age-associated diseases such as Alzheimer’s disease, Parkinson’s disease, and type 2 diabetes in humans and experimental animal models.1b,1d The brain is highly dependent on glucose as a fuel for the production of energy (ATP), but is also capable of using ketones as an alternative fuel.1c MCTs are converted to ketone bodies by the liver and, to a lesser extent, by the brain (astrocytes).1 In a study of Alzheimer’s patients,2 MCT supplementation was reported to improve cognitive function in a subset of patients who were negative for the apoE4 allele. (As you may recall, having an apoE4 allele increases the risk in humans of Alzheimer’s disease, as well as increasing brain damage from trauma; having two apoE4 alleles is associated with an even greater increased risk.) The researchers2 also found that cognitive improvement was correlated positively with brain levels of beta-hydroxybutyrate, a ketone body, which was increased by consumption of MCTs. A study of type 1 diabetics3 showed that MCT injection could reverse impairment of cognition by hypoglycemia as measured by diverse tests.

Other studies have also reported neuroprotection and cognitive improvement in patients with Alzheimer’s and Parkinson’s disease or animal models of these diseases by treatment with ketone bodies (such as beta-hydroxybutyrate that is produced during the metabolism of MCTs).3b,3c,3d

The performance of the “landmark discrimination learning protocol” used in the aged beagle dog study1 was reported previously by the same authors in two separate studies4,5 to be sensitive to age as well as to “a variety of interventions, including maintenance on an antioxidant diet and treatment with a combination of lipoic acid and acetyl-L-carnitine.”

Some of these tests were quite complex. For example, in one version, the dogs are trained to select the odd item out of three objects. In this study, this test was used with the addition of up to three other “distractor” objects to make the discriminations even more difficult. The dogs made fewer errors in a later test when the same single distractor object was used in an earlier test. The control aged dogs performed more poorly in this test when there were two or three distractors in the same and different tasks.

The MCT supplement was provided as 5.5% of the test diet (roughly equivalent to 1 to 2 tablespoons of MCT oil per day for a human); the controls had the same diet (regular dog kibbles) but without the MCT. At this level of supplementation, the production of ketones was well below the ketone levels induced by chronic starvation in dogs.1 MCT oil makes a very stable oil for salads and baking that is not readily oxidized and has a high smoking point; its boiling point is too low to use for frying, though.) Unlike most edible oils, MCT oil is mostly burned for energy rather than being converted into body fat.

References

1. Pan et al. Dietary supplementation with medium-chain TAG has long-lasting cognition-enhancing effects in aged dogs. Br J Nutr 103:1746-54 (2010).
1b. Sato et al. Insulin, ketone bodies, and mitochondrial energy transduction. FASEB J 9:651-8 (1995).
1c. Mingrone and Castagneto. Medium-chain, even-numbered dicarboxylic acids as novel energy substrates: an update. Nutr Rev 64(10):449-456 (2006).
1d. Constantini et al. Hypometabolism as a therapeutic target in Alzheimer’s disease. BMC Neurosci 9(suppl.):S16 (2008) doi:10.1186/1471-2202-9-S2-S16.
2. Reger et al. Effects of Beta-hydroxybutyrate on cognition in memory-impaired adults. Neurobiol Aging 25:311-4 (2004).
3. Page et al. Medium-chain fatty acids improve cognitive function in intensively treated type 1 diabetic patients and support in vivo synaptic transmission during acute hypoglycemia. Diabetes 58:1237-44 (2009).
3b. Henderson. Ketone bodies as a therapeutic for Alzheimer’s disease. Neurotherapeutics 5(3):470-80 (2008).
3c. Kashiwaya et al. D-beta-hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s disease. Proc Natl Acad Sci USA 97(10):5440-4 (2000).
3d. Gasior et al. Neuroprotective and disease-modifying effects of the ketogenic diet. Behav Pharmacol 17(5-6):431-9 (2006).
4. Milgram et al. Landmark discrimination learning in the dog: effects of age, an antioxidant fortified diet, and cognitive strategy. Neurosci Behav Rev 26:679-95 (2002).
5. Milgram et al. Acetyl-L-carnitine and alpha-lipoic acid supplementation of aged beagle dogs improves learning in two landmark discrimination tests. FASEB J 13:3756-62 (2007).


© 2010 by Durk Pearson & Sandy Shaw

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