The way to convert doses from animal studies to humans is to do it based on relative caloric or water intake. Water consumption is based on calorie consumption due to respiration, except humans that work enough to sweat can throw the water conversion off. Most nutrients are studied at a level of 0.2% to 0.5% of daily water or food intake. In humans this works out to be about 0.2% to 0.5% of 1 kg of food or 1 liter of water per day which is 2.5 to 10 grams of the nutrient. (1 liter per non-sweating person is closer to normal than eight 8 oz glasses per day which they finally realized was absurd after 30 years of the 8 of 8oz nonsense. )
But usually you see data in mg nutrient per kg body weight of rat or mice. Mice are about 30 grams and rats about 300 grams. You can find many studies giving 10 mg/kg/day to mice or rats for many nutrients. (It can range from 1 to 200 mg/kg/day.) You would think that to convert this to a human dose you would multiply 10 mg/kg times 70 kg person which gives 700 mg/day. But there is an adjustment: for mice you divide this by 7, and for rats divide by 4. So it's 100 mg/day for a 70 kg person if it was a mouse study and 175 mg/day if it was a rat study. The reason for the reducing it is because larger animals have a slower metabolic rate per kg body weight. The reducing factor is found by (human kg)/(animal kg) raised to the 0.25 power. EPA and FDA still use 0.33 power which was found to be wrong about 50 years ago, but they stick with it because they are normally investigating the toxicity of pollutants and pharmaceuticals and the 0.33 factor gives a margin of safety. But for nutrition comparison, 0.25 power should be used because it is more accurate and the safety of plant compounds is about 100,000 times better than pharmaceuticals. At least that's the ratio of the number of people killed each year from each, 100,000 pharmaceutical deaths when taken as directed verses 1 nutritional supplement death. The 0.25 factor results in slightly higher doses than FDA's 0.33. Study trials use these considerations to determine how much of a nutritional supplement to give to people for the first time, using animal data as the starting point.
To demonstrate how closely animals and humans compare: RDA's or RDI's for mammals are consistent, having roughly 1/3 of the RDA's 3x lower in other mammals than in humans, 1/3 are about 3x higher, and 1/3 about the same. The list of RDA/RDI's for all mammal is nearly the same. The macronutrients compare more closely. Specific compounds might be further off than the RDI's. But if they are similar to RDI errors, then if I conclude I need 100 mg of a nutrient to compare to the mice or rat study, it might be that I need closer to 300 mg or 30 mg. As with RDI's, being in the ballpark is a major step forward, and 100 mg is definitely in the ball park. But PD is very much like cancer, spreading to adjoining cells and compromising mitochondria, causing it to burn sugars anaerobically. It is no coincidence that green tea extract and grape seed extract work great in mice and rats for both cancer and PD. And in cancer, dose is everything: for example, with green tea extract and grape seed extract, cancer grows 50% slower instead of 25% slower if you double the amount of green tea or grape seed extract mouse or rat is getting, like a grandmother drinking 20 cups of green tea instead of 10, or eating 1/2 pound of grape seeds per day instead of 1/4 pound. So thank goodness for the extracts. So I might conclude 100 mg is enough, but 300 mg might be twice as healthy, if it doesn't rot my stomach from too many bitter powders, as you'll see from my list below.
Yesterday and today I worked on flavonoid extracts. To figure the dose I need, I needed to see what dose was used in mice models of PD, then see what concentration of each compound is found in tangerine peel, then look at what is available for sale, and adjust for human body weight. The mice studies used about 10 mg/kg for several of these flavonoids, so I want about 100 mg/day as I detailed above. I am talking about the compounds that specifically raise ghrelin and work in mouse models of PD: tangeretin, hesperidin, and nobiletin. Hesperidin was used at much higher levels than the other two in the PD models, but it is also in much higher concentrations in the tangerine peel. So if I get enough of the others, I get about the right amount of it. Tangerine peel has about 500 mg/kg (500 ppm) nobiletin which is 0.05%. Extracts are sold with 10% nobiletin or 10:1 concentration. The 10:1 will be only 0.5% nobiletin and cost $50/kg. The 10% has 20x more and cost twice as much. But I do not know the effects of their 10% extraction process on the other compounds. Tangerine peel extract standardized to 10% nobiletin could have anywhere from 10% tangeretin to 1% based on tangerine peel data I've seen, but it could be have a lot less because they may be selling a separate 10% tangeretin product, or otherwise neglecting the tangeretin due to concentrating the nobiletin. But typically pick only 1 component to measure because of the expense and complexity of trying to measure the others, not because the ratio of the others has been reduced.
ANYWAY, I got the 10:1 product, having 0.5% of my nobletin and since tangeretin is probably about 0.15%, I'll shoot for 200 mg/day of nobiletin which would be about 60 mg/day tangeretin and plenty of hesperidin. 200 mg/0.5% = 40 grams/day of 10:1 tangerine peel extract. This means the $50 for 1 kg will last 25 days. Will it mix in a blueberry smoothie? I'll find out. But the 10% nobiletin product looks a LOT more doable, requiring only 2 grams a day, about 2 large pills.
The bitter orange extract powder product can be found standardized to 10% naringin, but then I found a grapefruit extract can do 10% naringin at 1/2 the cost. It has shown major promise in PD animal models, and in many other things. This is the grapefruit compound that amplifies the effects of some drugs and is believed by some to help weight loss. It's strange how "stimulants" keep popping up for PD.
Dried blueberries are about 0.4% anthocyanins and the available extracts are 25% (62x concentration), so to get the 2 cups (300 g) per day human equivalent found very useful to the balance and cognition in mice, I will need 300/62 = 5 g. Therefore the $200 I spent on 1 kg will last 200 days. Other studies put 0.2% to 0.3% anthocyanins in water or food, which works out to 2 to 3 grams for 1 kg food or 1 L water for a human, so 5 g is about right.
If you found the above too painful, here is the summary (and for my future reference):
tangerine extract 10:1, 40 g/day, or more preferable:
tangerine extract 10% nobiletin, 2 g/day ($150/kg, $0.30/day)
blueberry extract 25% antho's: 5 g/day ($1/day)
green tea extract 1 to 2 g/day (two to four 500 mg pills, lot of caffeine)
black tea extract, 0.5 to 1 g/day (2 to 4 pills, not cheap)
apple extract 80% polyphenols 3 g/day (to simulate 200 mg/kg in mice) $200/kg, $0.75/day
naringin 98% 1.4 grams/day (to simulate 80 mg/kg in rats) $120/kg, $0.17/day
98% tangeretin looked great, but it is $7000/kg.
Broccoli and strawberries are two other good foods to eat. All of the extracts above might be combined with their whole fruit to be more palatable, and to help in absorption and correct metabolism. For example, more sugars in the blood stream might help them cross the blood brain barrier better.
B1 and madopar experience
Is ELDEPRYL the reason for my PD not getting vorse the last 15 years?
