Lifestyle and diet "cocktails".
Can diet and lifestyle impact disease risk? Probably!. Most people who get Alzheimer’s diseases have no genetic link ad epidemiology, trials and animal studies argue that non genetic risk factors can impact vulnerability
Appears to increase risk are:
- Prior Head Injury after puberty with loss of consciousness
- insulin-resistant diabetes
- High Cholesterol and othe cardiovascular related factors.
Appears to reduce risk are:
- Number of years in schoo
- Diet high in fish oil or docosahexaenoic acid
- Diet high in fruit and vegetables.
- Prior intake of fish oil or fish 3 x week
- Intermittent low dose NSAID use 2 years prior
There are many choices to take supplements for. Efforts to suggest cocktails are difficult because cocktails in our lab have often failed, possibly because they counteract effects on different aggregates. For example if tau aggregates are in equilbrium between soluble and insoluble a compound that reduces soluble added to one that reduces insoluble would likely require an increased concentration of the factor reducing soluble. Another reason for failure of cocktail is competitive binding. We do know that some cocktails work, Such as DHA and fisetin. Curcumin and DHA.
We are investigating other cocktails. Here we recommend a dosing paradigm to start with.
DHA. DHA is lost from neuronal membranes in the disease process, preventing the brain from functioning normally. Its reduction leads to problems beyond membrane integrity by impairing normal signalling.For prevention DHA from fish oil or salmon oil (which has slightly higher DHA than EPA and may be superior) could be sufficient ,but some level of pure DHA should be taken so the ratio of EPA: DHA is greater than one as EPA can compete for DHA absorption. Discussion of detail of how much to take, how much it typically costs and where to buy are discussed here Curcumin Page , Derivatives of curcumin such as J147 developed by Drs. Schubert and Maher at the Salk Institute, have additional effects and are in the pipeline for drug development.
Other dietary components in the pipeline with excellent safety profiles and strong rationale.
One interesting compound is a component of strawberries, called fisetin. -The exact dose awaits clinical trials and further clinical pharmacokinetics data. This can be purchased at Fisetin "Cognisetin"100 mg x 30 capsules and about $14. Dosing 2 capsules daily (round up or down depending on body weight). The total cost is about $28 per month.Fisetin is a powerful antioxidant, so do not take with medicine using an oxidation
mechanism. As always, consult your physician.
Vitamin C-time release
The strongest genetic risk factor for Alzheimer is ApoE4. Data suggest that subjects with ApoE4 may respond differently to therapeutics. For example DHA has different effects on subjects with ApoE4 than it dose with ApoE3. In fact data suggests that DHA works very poorly in ApoE4 subjects. One reason may related to the excessive oxidative damage in the ApoE4 brain. Long chain fatty acides such as DHA are readily oxidized and depleted from membranes connecting neurons, leading to a depletion of DHA in the brain. The problem with increasing DHA intake is that it oxidizes in the brain. Surprisingly Vitamin E is not a good antioxidant protecting DHA. It has been shown that Vitamin C can reduce oxidation from high fish oil intake in normal healthy male volunteers. One problem with taking vitamin C is that it can become a Pro-oxidant as it does its work, picking up free radicals. To avoid this time/sustained released vitamin C (eg. 500 mg) is available at most grocery and drug stores or can be purchased Sustained release Vit C, costing only $4 per 100 capsules. One per day should suffice.
Supplements for mitochondria-Coenzyme Q10?, Coenzyme Q10? ketogenic diet?
One major problem with neurodegenerative disease, is that the energy costs of an injured tissue is higher than can be supplied and leads to mitochondrial damage, further limiting ATP (the direct energy source). Further the reduction in the normal response regulating energy of the cell is damaged (responding to signals like insulin that import the glucose needed for ATP generation). This is particularly a problem in ApoE4 subjects.
Factors such as alternate sources of energy such as ketones are proposed. However the ketogenic diet is harsh and cannot be tolerated in adult and only a few months in children with epilepsy. There are at least two alternatives: Atkins Diet and the Coconut Oil diet. Clinical trials are ongoing for effect of coconut oil, but the down side is that diets rich in saturated fats increase risk for AD. Therefore an Atkins Diet may be a better choice.
No trial has been done on Coenzyme Q10, and trials done by ADCS by Dr. Galasko show that cocktails containing Vit E, Vit C alpha lipoate and Coenzyme Q10 did not alter the major two CSF biomarkers tau and amyloid. However there is still strong rationale for further testing of coenzyme Q10, particulalry for ApoE4 subjects, because of its beneficial effects in a similar disease Huntingtins disease on mitochondrial function.