Today's topic starts out with spinach (Spinacia oleracea).

This green, leafy vegetable has a unique rep. At least in the U.S., mothers ply their kids with it because spinach is said to be loaded with iron, a source of health and strength. Popeye the Sailorman's refrain goes: "I'm great at the finish 'cause I eat my spinach."

Then there was the classic 1928 New Yorker cartoon, in which a distraught mom cajoles her highchair-bound child: "Darling, I say it's broccoli!" To which Darling comes back, "I say it's spinach, and I say the hell with it!"

The iron-in-spinach mystique is something of a myth. In one version, which ran in the July/August 1998 issue of BeSlim Magazine, a typo was made by the assistant to an American nutritionist who typed in that spinach had 34 milligrams of iron per 100 grams, when the correct figure was supposed to be 3.4 mg per 100 grams. Unfortunately, this error escaped correction, and the 34 mg figure was widely published.

Spinach does indeed contain a lot of iron, but that health-giving ferrous metal isn't much use to humans because the veggie also packs a different chemical, phytate by name, which blocks iron from entering the bloodstream.

One-Third Of World's People Starved For Iron

Spinach aside, iron blockage afflicts a hefty proportion of the human race. Approximately 2 billion people, mainly menstruating women and growing children, suffer iron deficiency. In the U.S., an estimated 9 million people are iron-deficient. This lack is associated with an increased risk of poor pregnancy outcomes in women and impaired cognitive development in young children, plus retardation of central nervous system maturation. In some developing countries, public health workers give pregnant women daily supplements containing 120 mg of iron to prevent and correct gestational iron deficiency. This dose of iron, which is 10 times the normal dietary intake of the metal, can cause adverse gastrointestinal side effects.

Heme, the oxygen-carrying, rust color-furnishing ingredient of hemoglobin, is a major functional form of iron in the cell. There it's synthesized in the mitochondria by an enzyme called ferrochelatase, which inserts ferrous iron into that organelle's Complex IV. Heme's synthetic pathway depends on essential micronutrients, mainly vitamin B6, lipoic acid (present in yeast and liver extracts) plus copper and zinc, along with heme's cargo of iron.

About 10 percent of the U.S. population ingests less than 50 percent of the recommended daily allowance for B6; 25 percent of menstruating women less than 50 percent of the RDA for iron. That's the bad news. The worse news is that heme synthesis in the body is exposed to deficiency by imported lead, aluminum and other environmental toxins. Previous morphological and biochemical studies have shown that iron deficiency causes mitochondrial dysfunction in heart, skeletal muscle, liver and blood cells.

Iron deficiency also occurs in the elderly as well as in Alzheimer's disease (AD) patients. A paper in the Proceedings of the National Academy of Sciences (PNAS), released online Nov. 5, 2002, is titled: "Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging." Its senior author is the eminent molecular biologist and biochemist Bruce Ames, who discovered the Ames test for bacterial immunogenicity and carcinogenicity in 1971. The paper's first author is principal investigator Hani Atamna.

"In this study," they began, "we tested the hypothesis of a possible role of heme deficiency in neuronal decay. Many of the phenotypic changes seen in heme-deficient cells are also seen in the aging brain and are even more pronounced in neurodegenerative diseases such as AD. In addition, brain cells that were heme-deficient failed to differentiate or to complete a successful cell cycle in our experiment, which suggests a unique function of heme that is beyond the classic perception of heme in cell biology.

"The loss of brain cells seen in normal aging, and in disorders such as AD, may result from a simple iron deficiency," the PNAS article's co-authors suggest. They note that the primary reasons behind this neurodegeneration remain unknown. Their paper postulated that age-related heme deficiency might be a factor in the death of brain cells. To check this hypothesis, they blocked heme synthesis (by incubating N-methylprotoporphyrin for six days into their in vitro brew). They tested three types of cultured brain cell lines - two human (neuroblastoma and astrocytoma), and one from hippocampal cells in rat brains.

They report that heme deficiency altered metal homeostasis in astrocytoma but not in neuroblastoma. However, it did compromise proliferation or differentiation of both human cell types. Blocking heme synthesis, they observed, led to metabolic changes within the cells that were strikingly similar to those found in AD. When they tried to prompt the cells to multiply, the heme-deficient ones died after 48 hours. This indicated that heme synthesis plays an important role in the synthesis of mammalian brain cells. It decreases mitochondrial complex IV, activates nitric acid synthase (which generates NO), altered amyloid precursor protein (APP - the mother molecule of Alzheimer's disease senile neuritic plaques), and corrupts iron and zinc homeostasis.

"Heme-deficient cells," they point out, "make abnormal forms of APP, which is processed to amyloid-b, a hallmark peptide in the pathology of AD. Complex IV," they add, "seems to be the most sensitive to heme deficiency, which leads to mitochondrial decay."

Heme Deficiency: Preventable, Correctable

The paper points out that "iron and B6 deficiencies are especially important because they are widespread, but they are also preventable with supplementation. Thus heme deficiency or disregulation may be an important and preventable component of the neurodegenerative process."

It made the point, "The metabolic events that initiate mitochondrial decay, neuronal death and the neurodegeneration caused by AD are unknown." But it added: "Iron accumulates in cells and a marked increase in zinc and iron associated with extracellular plaques is found in AD patients, suggesting a disruption of metal homeostasis. The heme-deficient astrocytoma and neuroblastoma cells accumulate iron, probably in the mitochondria because corruption of heme synthesis causes iron to accumulate in this organelle."