Harvard Health Letter

Nutrition's dynamic duos

We spend a lot of time fretting about individual nutrients, but often they work in tandem.

Nutrition guidelines and labels sometimes seem to have been written one nutrient at a time. We're advised to get this amount of that vitamin and that amount of this mineral. Separating out nutrients this way makes the guidelines relatively easy to understand and probably does help us avoid the classic diseases of nutritional deficiency, such as scurvy (not enough vitamin C) or pellagra (not enough niacin).

But good nutrition — and the way in which in our bodies absorb and process nutrients — is a much bigger puzzle than a nutrient-by-nutrient tally sheet suggests. Most nutrients don't fly solo: they interact, join forces, cancel each other, jockey for position on metabolic pathways. One reason food is so often nutritionally preferable to pills or supplements is that food contains a mixture of nutrients, so we benefit from their interactions with each mouthful.

The following is a list of nutrients that work in pairs. It's just a sampler, and far from a complete catalog. Even so, it may help inform some food choices — and give just a taste of the cruel complexity of the nutrition lurking behind guidelines and easy-to-read labels.

Vitamin D and calcium

Like most nutrients, calcium is absorbed primarily in the small intestine. If large quantities are present, much of the bone-strengthening mineral diffuses across the inner lining of the intestine on its own. But in smaller amounts, the mineral gets absorbed with active assistance from vitamin D and several of its metabolic offspring. D also lends a helping hand in the absorption of phosphorus, another mineral important to keeping bones strong and healthy, and magnesium. The evidence that D may have wide-ranging benefits, including offering some protection against heart disease and some forms of cancer, has piled up lately. Some of these benefits may be the result of the vitamin's absorption-related duties, but it may have a more direct effect on disease processes and the immune system than previously believed.

Right now, the official nutrition guidelines recommend that adults get 1,000 milligrams (mg) of calcium and 400 international units (IU) of vitamin D daily. For older adults, it's a bit more: 1,200 mg of calcium starting in your 50s and 600 IU of vitamin D starting in your 70s. To give you an idea of how much that is, an 8-ounce glass of milk contains 300 mg of calcium and, because of fortification, 100 IU of vitamin D.

There's debate these days about whether to revise the recommendations to reduce the goal for calcium intake (or at least de-emphasize it) and raise the goal for vitamin D (to 1,000 IU or even more).

Sodium and potassium

About 90% of the sodium we ingest comes in the form of sodium chloride — salt, in common parlance. Sodium and chloride are essential nutrients — we need them to maintain fluid levels in the body — but the average American consumes thousands more milligrams of sodium daily than he or she will ever need. Excess sodium interferes with the natural ability of blood vessels to relax and expand, while also encouraging the body to hang on to water, so blood volume increases. "Uptight" blood vessels with more blood flowing through them: that's a formula for cardiovascular woe. Blood pressure goes up, and with it, the chances of having a stroke or heart attack.

But potassium, because it encourages the kidneys to excrete sodium, counters the harmful cardiovascular effects of sodium surplus. Many studies have shown a connection between high potassium intake and lower, healthier blood pressure. Several have dug a little deeper and found that the potassium-to-sodium ratio may be more important than potassium — or sodium — alone, although precisely what the ratio should be is uncertain.

According to the current guidelines, American adults are supposed to get 4,700 mg of potassium and 1,200 to 1,500 mg of sodium daily, which works out to a ratio of somewhere between four-to-one and three-to-one. The average American intake is about half that amount of potassium (2,500 mg) and at least double that amount of sodium (2,500–7,500 mg).

But time for a reality check: how many people are going to do the math and keep track of their potassium-sodium ratio for the day? It's enough for most of us just to count calories.

Fortunately, the take-home message is simpler. Almost all of us need to have more potassium in our diets and a whole lot less sodium. And the best way to do that is consistent with the standard good nutrition playbook: load up on fruits and vegetables (prime sources of potassium) and cut back on cookies, salty snacks, fast foods, and ready-made lunches and dinners (prime sources of sodium).

Vitamin B12 and folate

Vitamin B12 and folate form one of nutrition's more estimable couples. They work together to support some of the most fundamental processes of cell division and replication. They also metabolize homocysteine together. And folate, which is itself one of the eight B vitamins, depends on B12 to be absorbed, stored, and metabolized. All this togetherness, despite the fact that these two nutrients hail from different sides of the animal-plant divide: vitamin B12 occurs naturally in meat, eggs, milk, and other foods of animal origin, while the best natural sources of folate include hard-core veggie fare like leafy green vegetables, beans, and legumes. Fortification has blurred these lines. Breakfast cereals with added vitamins and minerals contain B12, and in the United States, by law, cereal grains are fortified with folate. Indeed, because of fortification, it's fairly easy to get the recommended amounts of B12 (2.4 micrograms) and folate (400 micrograms) by eating a reasonably well-balanced diet.

Strict vegans, who shun all animal-based products, may sometimes struggle to get enough B12. But for the most part, it isn't for lack of intake that B12 deficiency develops. It typically occurs because of shortages of substances inside the digestive system. Some people lack intrinsic factor, a protein made by stomach cells that's needed for B12 to be absorbed further down the pike, in the ileum, the end portion of the small intestine. And many older people secrete fewer of the gastric juices that break down B12-containing compounds because they have atrophic gastritis, an inflammatory condition that affects the lining of the stomach.

Folate deficiencies occur for a number of reasons, including poor diet, too much alcohol (alcohol interferes with the absorption of folate), and B12 deficiency, because folate needs B12 to be metabolized.

Deficiency in either or both vitamins may cause macrocytic anemia, a form of anemia that results in enlarged red blood cells.

Remedying a B12 deficiency can be pretty straightforward. You can get injections every few months or take a pill daily. Even if you're low on intrinsic factor or have atrophic gastritis, the dose in the pills is often large enough (1 mg) that an adequate amount of the vitamin gets absorbed.

Folate deficiencies can be corrected with multivitamins or folic acid pills. In fact, folate from fortified food or a pill is absorbed and metabolized almost twice as well as folate found naturally in food. Similar to the B12–intrinsic factor dynamic, if you ingest large amounts of folate, some manages to get absorbed even if levels of its B12 partner are low.

There is an interesting twist to the B12-folate story. Doctors often stumble upon the existence of a B12 deficiency by finding macrocytic anemia after ordering a routine blood test. Tests for folate and B12 aren't usually ordered. When someone with a B12 deficiency takes folic acid supplements, those supplements can make the macrocytic anemia go away — or prevent it from happening. But that eliminates the most common clue to B12 deficiency, and the deficiency itself may continue. B12 deficiencies cause neurological problems, which range from mild tingling sensations to memory loss, in addition to anemia. So people live with neurological problems that might have been easily and inexpensively treated with some extra B12.

Zinc and copper

We associate copper with pennies, wire, and pans, but it's also an essential nutrient. Zinc is a little more familiar as an edible substance, partly because people take zinc lozenges in the belief that extra zinc shortens the duration of a cold (the evidence is mixed on whether it actually does). Adults are supposed to get 900 micrograms of copper daily. The daily zinc goals are 11 mg for men and 8 mg for women. Neither mineral is rare in the American food supply, so copper and zinc deficiencies don't loom large in the nutritional worriment — with a couple of interesting exceptions.

Copper and zinc compete for absorption sites in the small intestine. If there's a lot of zinc around, copper tends to lose out and a copper deficiency may develop.

Some people in the early stages of macular degeneration, an eye condition that can lead to blindness, are prescribed a special vitamin-mineral combination, called AREDS, which has been shown to slow down progression of the disease. The AREDS pills include 80 mg of zinc, enough to cause a copper deficiency, so 2 mg of copper were added to the pills.

Another possible source of zinc overload is, of all things, denture cream. A report published in 2008 in Neurology described four cases of denture wearers with neurologic abnormalities. Their problems were ascribed to a copper deficiency from zinc exposure that came from using very large amounts of denture creams. A neurologist at Harvard-affiliated Beth Israel Deaconess Medical Center diagnosed a similar case of denture cream–induced neurologic abnormality in 2009.

Niacin and tryptophan

Niacin is one of the B vitamins, although it rarely goes by its B vitamin moniker, B3. These days, it's probably best known for its cholesterol effects. Large doses (500 mg to 1,500 mg per day) lower "bad" LDL cholesterol and increase "good" HDL cholesterol. Those pharmacological doses far exceed the amounts needed for nutritional purposes. The daily niacin requirement is 16 mg for men and 14 mg for women.

Amino acids are the building blocks of protein, and tryptophan is one of nine that we need to ingest because the body doesn't synthesize them on its own. Tryptophan is important for several reasons, but chief among them is its role as a supplier of niacin, courtesy of some rather complicated metabolism. So one way to avoid niacin shortfalls is to eat foods that contain a lot of tryptophan. Chicken and turkey are high on that list.

Pellagra, now held up as the classic disease of niacin deficiency, was once thought to be caused by a tryptophan deficiency. The disease, which causes a bad rash, diarrhea, and dementia, was common in the American South in the early 20th century. How researchers traced it back to a niacin deficiency and a corn-based diet is one of the great tales of nutritional epidemiology.