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curs. (KBs are a byproduct of fatty acid metabolism.) So even though the Moreover, if AD stems from a diet and lifestyle
brain is starving for fuel, KBs will not be produced in sufficient quantity. at odds with what our evolutionary history has
The end result for an AD patient is that the brain is not metabolizing glu- prepared us for, then an abandonment of refined
cose effectively and no alternative fuels are available. For neuronal cells and chemically altered foods and a return to a
that have such enormous energy requirements, the consequences of this more “primitive”-type diet would also likely be
disruption in fuel supply are devastating. protective. Specifically, if the initial pathogenesis
If ketones are the brain’s primary fuel source under conditions of of AD comes from peripheral hyperinsulinemia,
reduced glucose availability, then AD patients should show improvements there is reason to believe that restriction of di-
in cognitive function on a ketogenic diet or with administration of exog- etary carbohydrates should be frontline therapy
enous ketones. This has been demonstrated in randomized, double-blind, for AD. The therapeutic and neuroprotective
placebo-controlled studies. In two studies, oral administration of KBs effects of ketone bodies are so effective, in fact,
via medium-chain triglyceride (MCT) drink mixes resulted in improved that one researcher suggests a drawback of the
performance on cognition tests compared to placebo, and this was achieved modern, carbohydrate-heavy diet is that it is
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even in the absence of dietary carbohydrate reduction. “keto-deficient.”
In a study involving dietary ketosis via a low carbohydrate diet (less A classical ketogenic diet—with a stag-
than 10 percent of total calories), compared to subjects on a 50 percent gering 70-90 percent of total calories coming
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carbohydrate diet, the low-carbohydrate subjects demonstrated better per- from fat—might not be necessary. Classical
formance on memory tests, with higher scores being correlated to higher ketogenic diets restrict protein as well as carbo-
serum KB levels. A study using cultured mouse hippocampal cells showed hydrate, since 48-58 percent of the amino acids
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that addition of the KB β-hydroxybutyrate (β-OHB) to cells exposed to Aβ in dietary proteins can be glucogenic, thereby
resulted in no decrease in the numbers of dendrites or total neurons—two undermining the purpose of a diet intended to
of the noted pathological changes in AD. Addition of β-OHB at a 4 mM generate a high amount of ketones and limit glu-
concentration—achievable on a very low carbohydrate diet—doubled cose as much as possible. As therapy for AD,
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the surviving number of cells and actually increased dendritic growth. however, simply lowering carbohydrate intake to
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Analyses of brains of people who have aged free of cognitive decline have a point where some ketones are generated and hy-
shown that a loss of neurons can be compensated for by an increase in perinsulinemia is corrected could have positive
dendrites of the remaining neurons so there is no net loss of synapses. 49 effects just by easing the metabolic burden on
If the primary metabolic change that occurs during fasting or a the brain. That is, one could reap the “benefits”
ketogenic diet is a wholesale shift away from glucose and toward fatty of fasting (enhanced insulin sensitivity, reduced
acids and ketones for fuel, with the resultant lowering of blood glucose oxidative stress, reduced AGE formation) by
and insulin levels and restoration of insulin sensitivity, then reduced simply reducing carbohydrate intake to prevent
carbohydrate consumption should lead to similar neuroprotective effects. chronic systemic hyperglycemia. Moreover,

THERAPEUTIC INTERVENTION FOR ALZHEIMER'S DISEASE

Current Alzheimer's disease (AD) therapies are typically piecemeal approaches aimed at treating individual symp-
toms, rather than addressing the underlying causes of the disease. One drug manufacturer created a pharmaceutical
drug to inhibit the enzyme that creates Aβ from the amyloid precursor protein. Phase III clinical trials had to be stopped
because results were so damning against this treatment. Measures of cognition and ability to complete daily living tasks
were significantly worse for patients receiving the drug than the placebo. Yet again, here is evidence that Aβ is not a
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causal factor. Production of Aβ is a normal process and there is no evidence that AD patients overproduce it. It becomes
pathological only when—due to peripheral hyperinsulinemia—it is not degraded and cleared as it should be.
Several authors have proposed administering exogenous ketone bodies via pharmaceutical MCT preparations. While
this provides the brain with an alternative fuel and has been shown to improve cognitive function, it does nothing to ad-
dress the myriad other issues attendant with the metabolic derangement that is likely the root cause of AD. The cognitive
decline seen in AD is not a disease in itself; it is the result of a lifetime of accumulated dietary and environmental insults,
which in older age finally overwhelm the brain’s capacity to protect and heal itself. Administration of KBs would neither
alleviate hyperinsulinemia nor restore insulin sensitivity at the BBB. MCTs could certainly be a powerful adjunct to a
reduced carbohydrate diet, which would reset the metabolic machinery, ease oxidative stress, and reduce glycation. In
the absence of dramatic dietary overhaul, however, the administration of KBs is akin to bailing water out of a leaky boat
without stopping to patch the hole: you merely manage the effects while the root cause continues wreaking havoc.

42 Wise Traditions SUMMER 2014 Wise Traditions

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