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Just a point to think about in determining the timing of Sinemet and food. The theory and instructions on timing are acknowledged as take standard Sinemet on an empty stomach BEFORE food and Sinemet CR WITH food. However, concerning Sinemet CR, I had for a long time been taking it 30 mins BEFORE food quite successfully. I then switched to taking it WITH food. Well, I was not doing so well this way but did not at first connect it with the change in sinemet/food timing because I was also coming off Eldepryl and attributed ALL the the problems to the Eldepryl withdrawal. I continued to do badly without the Eldepryl until I noticed, with the help of a diary and Brian Collins' charts, that on the occasions that I had taken a Sinemet CR and then not eaten for at least 30mins that I did not end up with the usual "between tablets gap". At around the same time I changed to a top neurologist specialising in PD and brought the subject up with him. I pointed out that even the manufacturers of the drug (I spoke to them by phone) insist that the CR formulation is designed to be taken WITH food. His comment was that food affects ALL Sinemet and that I try taking the Sinemet CR 40mins BEFORE meals. This small change in timing has made the world of difference to me. I take my 3 sinemet CR tablets at 4 hourly intervals and only now and again do I experience a gap lasting a short period. Taking them WITH food I ended up with longer "off" periods and, sometimes, hardly switched on at all in the afternoon. The strange thing is that I expected the tablet to "Go through faster" this way and run out quicker. Instead, the reverse is true, I stay on for longer. I believe that the reason this works better for me is as follows: A Sinemet CR for me lasts about 4 hours then fades rapidly at the 4 hour point. To take a Sinemet CR at this 4 hour point WITH food will delay the action of the new tablet allowing the blood plasma level to drop to a level low enough to cause problems and cause the "off" period. Taking the Sinemet CR at the 4 hour period WITHOUT food allows the tablet to start working more quickly and prevent the gap at the 4 hour point. Some conclusions I have reached based on all sources including personal experience are as follows: 1. Regular Sinemet...Yes undoubtedly, take without food. 2. Sinemet CR....Recommended taken with food. HOWEVER, bear in mind that if you are experiencing a 4 hour gap like I was, it COULD be that you might benefit by talking to your neurologist about experimenting with taking your CR BEFORE food and experiment with how soon afterwards you eat. YOU may find 10 or 20 mins before food works. 3. It is not STRICTLY accurate to say that Sinemet CR is unaffected by food. It IS designed to be taken with food and it is less affected by food, but if you think about it the active ingredients are the same as regular sinemet, it is just the construction and formulation which enables the sustained release, which differs. 4. The bio-availability (the amount the body can use) of Sinemet CR is, according to my neuro, only around 70% that of the regular Sinemet. 5. Everybody is different in requirements, digestion system, level of nausea experienced, etc, and what might not work at all for one person could be the brilliant answer for another. It may take time and experimentation to get it exactly right for you. Be patient and prepared to experiment. Good luck, Ernie Peters <[log in to unmask]>