In my opinion this paper published December 3 2008, is dynamite.
http://www.pubmedcentral.nih.gov/ar...i?artid=2604900
(edited to add link)
There are three main points I will highlight, though the entire paper time and again reinforces the view that Ketones are significantly beneficial to those suffering cognitive decline.
(One reservation is that patients with APoe4 gene do not appear to benefit from ketones.)
Salient points
1 Cognitive decline is signaled decades in advance of clinical symptoms.
"Therefore, it appears that glucose hypometabolism occurs in at-risk individuals decades before clinical symptoms of dementia are evident, and is unlikely to be due to cell loss. This has been examined in carriers of presenilin 1 mutations in cases of early-onset AD. Asymptomatic, individuals at-risk for early-onset AD were examined by magnetic resonance imaging and FDG-PET, and compared with normal matched control individuals [12]. Extensive reductions in CMRglu were found in the presymptomatic early-onset AD individuals in the absence of structural brain atrophy, suggesting again that cell loss is not a gross contributor to low FDG-PET signals."
2 MCT oil allows therapeutically useful blood ketone levels to occur without the necessity for classic Ketogenic diet.
This is significant because one of the main problems with the classic ketogenic diet is low compliance.
"Although the ketogenic diet and administration of other energy substrates have shown clinical efficacy in a variety of CNS disorders, these strategies are impractical for chronic use because of low compliance with high fat/low carbohydrate intake, unpalatable regimen, and poor tolerability to the high number of calories required to produce therapeutic levels of ketone bodies (90% of calories must come from fat). Therefore, a means by which to obtain high ketone levels, while allowing the patient to eat a relatively normal diet, has been under investigation.
AC-1202 (Axona™; manufactured for Accera, Inc., Broomfield, CO, USA) is a medium-chain triglyceride (MCT) that provides a simple and safe method to induce elevated plasma levels of ketone bodies. MCTs have chain lengths of 5 to 12 carbons and have a different pattern of absorption and utilization than long-chain triglycerides (LCTs), which make up 97% of dietary fats [46]. In LCT absorption, fatty acid chains are cleaved from the glycerol backbone by a lipase. These fatty acids form micelles, are absorbed and re-attach as glycerol, and the resultant triglycerides travel through the lymphatic system to the bloodstream and are stored in adipose tissue. In contrast, MCTs are absorbed without need for micelle formation (with no storage in adipose cells) and are transported to the liver for preferential oxidation by the portal vein [47]. The rapid oxidation of medium-chain fatty acids in the liver can give rise to the production of ketone bodies if sufficient doses of MCTs are provided. Medium-chain fatty acids enter the mitochondria as acyl-CoA moieties, where they undergo β-oxidation to form acetyl-CoA and acetoacetyl-CoA, which – if produced in excess – are combined to form 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA). HMG-CoA is then acted on by HMG-CoA lyase to form ACA and BHB. The liver cannot use ketone bodies and so they are released into the circulation to be used by other tissues (Figure 2)."
3 The positive effects of ketones are not universal. Carriers of ApoE4 do not benefit to the same extent.
"These preliminary findings suggest that acute elevation in BHB (beta hydroxy butyrate) levels may ameliorate the cognitive decline associated with impaired glucose metabolism in individuals without an E4 allele. These results are consistent with prior reports of ApoE4-related differences in insulin metabolism and cognitive effects of insulin administration [50,51]. "
However one can only hope that the information in this study, by shining a light on the mechanism of AD progression, may benefit all sufferers from AD at some future date.
Hypometabolism as a therapeutic target in Alzheimer's disease
Linear Mode
