For the past decade, we have increasingly learned that what and how much we eat are not the whole story. It’s also important to think about how fast it appears in the bloodstream. We are less than 500 generations after humans settled down to a farming existence, a span too short for major genetic changes to have taken place. Therefore we must consider how well our bodies handle whatever we eat. We can now, for the first time ever, easily ingest some food substances in amounts that are enormous compared to the amounts normally present in food.when this happens, these compounds temporarily reach blood concentrations far beyond ay available just from food, which are limited by the size of the stomach. Even good compounds become harmful at supernormal concentrations because the body, prepared only for amounts achievable for millions of years, cannot deal with the excess. Every substance, no matter how essential in nutrition, has a point beyond which it becomes harmful or even lethal. Vitamins A, D and K are well-known in this category, as well as all metals and, of course glucose. Excess of even water can be harmful.

Vitamin C. Unlike many other mammals, we cannot make our own, so we must eat it in food (or nowadays pills). Synthetic VC is identical with natural. It is widespread in foods, especially fruits and some vegetables. However, there is nothing in Nature that contains a high concentration. Therefore we must eat a fair amount of VC-containing foods to keep our bodies replete, which is important because it is the most important antioxidant, protecting us from numerous diseases. We need about 200 mg/day, which is normally ingested bit by bit all day. The blood level seldom moves far above or below the optimum. But now we can take all 200 mg at  once in a pill. This is enough for a whole day, but right after eating the pill, there is a huge influx into the bloodstream, a spike in concentration never before experienced by humans. The body is not equipped to handle it, and does several things: it send most of it out in the urine within an hour, and also up regulates an enzyme that destroys it, and doubtless other things we don’t yet know. The upshot is that most of the 200 mg is wasted, leaving us with insufficient VC for the rest of the day, and the unregulated anti-VC enzyme now attacks even normal amounts, reducing absorption of VC from food. Even more worrisome are the “things we don’t know about” , which might be anything at all.Those who choose to take supplemental VC should buy slow-release pills which permit absorption by the body only slowly, over a span of time long enough to prevent spikes.

Calcium. Like VC it normally appears in foods in moderate concentrations, and blood levels do not rise above a small bump. But when we eat a 500 mg pill, we get a huge spike that spreads out after a short time, but which meanwhile upsets the body’s metabolism. Very recently if has been reported that people who get their calcium from food are OK, but those who get it from pills are ~20% more likely to get a heart attack. How can a calcium atom in your blood know whether it came from food or a pill? It can’t, but your body can if there’s a spike. Must we then avoid calcium from supplements? No, we just have to take calcium only on a full stomach.By stretching out the time to digest, we stretch out the time it takes to absorb the calcium. That way, instead of a sharp tall spike, we get only a long-lived but relatively low bump in concentration. That’s exactly what happens with calcium in food, so by avoiding the spike we avoid the danger.

 Sugar. There is no natural source of pure sugar; the closest is honey. When we drink a sweetened soda, coffee or tea – and also when we eat white bread or white rice – all of the sugar and starch (which is polymerized sugar) appears in the blood as  sugar in a huge spike within a few minutes. This, repeated again and again, gives rise to diabetes and also (as recently discovered), to heart disease. Our bodies simply cannot handle these short but intense spikes. We speak of the glycemic index (GI) as the rate at which sugar or starch appears as sugar in the blood. A high GI appears as a narrow thigh spike; a low GI produces a broad low bump, which we can handle. There are two ways to deal with high GI: eat sugar and white starches in much lower amounts, and eat them only when there is a lot of fiber already in the stomach. Fiber temporarily binds sugar and thereby slows down its absorption, lowering not its amount but its GI. Therefore eat only brown bread and brown rice, whose fiber is protective, and eat sweets only in moderation and after a big meal, not before. Note that a low GI does not mean that we get less calories, only that we get them more slowly.

Carotene. This comes in foods only as a mixture of many types of carotene: alpha-, beta-, etc.-carotenes. They are all similar but not identical. This mixture is the only form of carotene we could eat since the beginning of time. Suddenly we are offered pure beta-carotene, an excellent antioxidant and therefore protective against degenerative diseases, e.g. cardiovascular, inflammatory and geriatric ones. Unfortunately our bodies cannot deal with pure beta-carotene in large amounts, and big pills that appear in the blood as tall spikes are somewhat detrimental to health. Yet moderately robust beta-carotene concentrations in the blood from food are beneficial. Why only from food? Because (1) the amounts cannot be too large owing to the limited capacity of the stomach, and (2) because beta-carotene from food is always admixed with all the other carotenes. Each carotene plays a different role in nutrition, as our bodies are not prepared for pure beta-carotene. The lesson: if you want carotene pills, make sure they’re small, taken on a full stomach, and also that they’re full-spectrum carotenes. Beta-carotene alone in small doses is safe because it’s converted to vitamin A in the body.

Vitamin E. The story is similar to that of carotenes. VE in Nature consists of eight similar but distinct substances, four tocopherols and four tocotrienols. All are excellent antioxidants that team up with VC for maximum protection. Nowadays most VE pills are only alpha-tocopherol which is cheap. Many recent studies have come up negative with VE because (1) the spikes from large pills are too high, and (2) the other seven components of VE are not there. In contrast, in populations getting their VE from food, high alpha-tocopherol blood levels correlate with good health, because it signals the presence of all eight components. The lesson: eat foods rich in VE, and if you want to insure yourself with pills, choose pills not too large that contain all eight components, eaten after meals.

There’s another special danger with  alpha-tocopherol. It can exist in two forms, d- and l-, which have the same structure but are mirror images of each other, just like left and right hands. Only the d-form occurs in Nature, but the cheapest form is dl-alpha-tocopherol, a 50-50 mixture of the two forms. In Nature, usually only one mirror form of anything is active, and the other is either inactive or even harmful. Whether l-alpha-tocopherol is merely inactive or actually harmful is not known. Therefore it is prudent to avoid ingesting l- or dl-alpha-tocopherol.

Drugs.  Pills containing drugs can also produce spikes in blood concentration. When spikes are dangerous, manufacturers make pills that dissolve slowly, to stretch out the period of absorption. Even these, however, do not provide perfectly smooth, constant blood levels because the rate of release of the drug, which is proportional to the pills’ surface are, is greater at first, diminishing as the pill gets smaller. Usually this is OK but sometimes perfect smoothness is required, and more complex formulations are needed. One way is to make the pills in layers like an onion, such that their rate of dissolution increases from outside to inside layers. Another is to encase the drug in an insoluble, harmless plastic shell pierced by a tiny hole that allows only slow exit of the drug during passage through the GI tract. Here there are no spikes at all. There is growing interest in these advanced drug delivery methods.