The Vitamin Cure – Discover magazine

The Vitamin Cure
Can common nutrients curb violent tendencies and dispel clinical
depression?

By Susan Freinkel
Photography by Dan Winters

DISCOVER Vol. 26 No. 05 | May 2005 | Biology & Medicine

Mental Machinery 
The brain and other complex mechanisms of the human nervous system
rely on 40 or so basic nutrients to run smoothly. The lack of any
one””be it zinc or magnesium, chromium or folic acid””can cause a
malfunction, leading to depression, irritability, or worse.

When pigs are penned in close quarters, some become so irritable
they savage their pen mates' ears and tails, a problem farmers call
ear-and-tail-biting syndrome. David Hardy, a Canadian hog-feed
salesman from the farmlands of southern Alberta, knew that behavior
well. Years of experience had taught him something else: All it
takes to calm disturbed pigs down is a good dose of vitamins and
minerals in their feed.

That came to Hardy's mind one November evening in 1995 when an
acquaintance, Tony Stephan, began confiding his troubles. His wife,
Deborah, had killed herself the year before after struggling with
manic depression and losing her father to suicide. Now two of his 10
children seemed headed down the same road: Twenty-two-year-old
Autumn was in a psychiatric hospital and 15-year-old Joseph had
become angry and aggressive. He had been diagnosed as bipolar, a
term for manic depression, but even with medication he was prone to
outbursts so violent that the rest of the family feared for their
lives.

The boy's irritability sounded familiar to Hardy. I don't know a
whole lot about mental illness, Hardy told Stephan, but I've seen
similar behavior in the hog barn, and it's easy to cure.

So the two men set out to create a human version of Hardy's pig
formula. They bought bottles of vitamins and minerals from local
health-food stores and spent nights at Stephan's kitchen table
concocting a mixture. On January 20, 1996, they gave Joseph the
first bitter-tasting dose. Within a few days, Joseph felt better
than he had in months. After 30 days, all the symptoms of his
illness were gone.

Stephan next turned to Autumn, whose mental state had been steadily
deteriorating for years. Now she was psychotic, convinced she had a
gaping hole in her chest from which demons emerged. Just released
from the hospital where she'd been on suicide watch, Autumn required
24-hour supervision to ensure she didn't hurt either herself or her
3-year-old son.

Stephan forced her to take the nutritional formula. After just two
days of treatment, her rapid swings between mania and depression
stopped. After four days her hallucinations vanished. "I remember
saying, `Oh my gosh, my hole is gone,' " she recalls. By week's end,
she felt well enough to quit all but one of her five medications.

Nine years later, both Autumn and Joseph remain symptom free,
medication free, and devoted to taking what they call "the
nutrients" each day. Autumn Stringam, her married name, is an
articulate woman with bright eyes who revels in being a full-time
mother to her son and the three daughters she's had since getting
well. "I don't feel I'm cured," she says. "I feel I've got something
that allows me to manage and have a normal, functional life””maybe
even better than functional."

It's easy to write off the Stephans' treatment as just one more
crackpot cure in a field rife with fraud and false hope. The
supplement they took has yet to be proved in large clinical trials,
while scientists who have studied it have been caught in the cross
fire between converts, willing to take the supplement on faith and
anecdotal evidence alone, and skeptics who look askance at all
alternative medicine. Yet the idea of treating mental disorders with
supplements makes sense, experts in the field say. Micronutrients
help build and sustain the brain's architecture and fuel its
biochemistry. They are critical in countless ways to the working of
cells throughout the body, including the brain. "We need 40
essential micronutrients in our diet””vitamins, minerals, and
essential fatty acids," says Bruce Ames, a biochemist at the
Children's Hospital Oakland Research Institute. Ames has explored
the impact of zinc and iron on brain cells. "If you don't have
enough of one, you're fouling up your biochemistry."

A number of diseases caused by nutrient deficiency, such as scurvy,
beriberi, pellagra, and pernicious anemia, display psychiatric
symptoms like irritability and depression. But while severe
deficiencies are rare in the developed world””when's the last time
you met someone with beriberi?””many of us fall short of getting all
the nutrients we need. In 1997 a British study compared the mineral
content of fruits and vegetables grown in the 1930s with the mineral
content of produce grown in the 1980s. It found that several
nutrients had dropped dramatically, including calcium (down nearly
30 percent), iron (down 32 percent), and magnesium (down 21 percent).

Some researchers suspect that even mild deficiencies can affect the
psyche long before any physical symptoms appear. Stephen
Schoenthaler, a sociologist at California State University at
Stanislaus, has been exploring the link between nutrients and mental
health by giving basic vitamin and mineral supplements to prison
inmates and juvenile detainees. Again and again, since the early
1980s, Schoenthaler has found that when inmate nutrition improves,
the number of fights, infractions, and other antisocial behavior
drops by about 40 percent. In each case, he has found, the calmer
atmosphere can be traced to the mellower moods of just a few
hotheads. The inmates most likely to throw a punch, he has
discovered, are the ones with the least nutritious diets and the
lowest levels of critical nutrients.

Schoenthaler's findings have been undermined by less than sterling
research methods: His papers have failed to describe the precise
methods by which he analyzed the inmates' blood. (In January, a
committee at his university recommended that he be suspended for a
semester without pay for academic and scientific misconduct in
later, unrelated research.) So in the late 1990s, an Oxford
University
physiologist named Bernard Gesch decided to put the

theories to a more rigorous test. Gesch divided 231 prisoners in one
of Britain's toughest prisons into two groups. Half were given a
standard vitamin and mineral supplement each day as well as fish-oil
capsules and omega-6 oil from evening primrose. The other half
received placebos. The results, published in 2002 in The British
Journal of Psychiatry, drew headlines on both sides of the Atlantic.
They were also almost identical to Schoenthaler's. Over the course
of approximately nine months, inmates taking supplements committed
about 35 percent fewer antisocial acts than the group taking
placebos. A few weeks after the study started, the prison warden
told Gesch that the administrative report that month showed no
violent incidents had occurred. "As far as he was aware, this had
never happened in the history of the institution," Gesch says.

Poor Man's Pharmacopoeia

A number of common nutrients may help alleviate mental illness when
taken in higher-than-normal doses. A few of the most promising
candidates follow.

FOLIC ACID
Folic acid is a B vitamin essential to mood regulation and the
development of the nervous system. Patients deficient in it appear
to respond poorly to antidepressants. In one 2000 British study, 127
patients taking Prozac were also given either 500 micrograms of
folic acid a day or a placebo. The folic acid group did
significantly better, in particular the women, 94 percent of whom
improved compared with 61 percent in the placebo group.

MAGNESIUM
It's long been known that magnesium can act as a sedative. Some
studies have also found magnesium deficiencies in patients with
depression, although the evidence is inconsistent. The mineral may
help other mood-stabilizing drugs work better. Researchers at the
Chemical Abuse Centers in Boardman, Ohio, found that combining
magnesium oxide with the drug verapamil helped control manic
symptoms in patients better than a drug-placebo combination.

CHROMIUM
Several studies have suggested that chromium picolinate may help
alleviate depression and improve the response to antidepressants. In
one small trial at Duke University, 70 percent of the patients who
were given chromium picolinate improved, while none of those given
placebos got better.

INOSITOL
This sugar molecule appears to make the brain's receptors more
sensitive to serotonin, one of the chemical messengers that mediate
mood. In a series of short-term placebo-controlled trials,
researchers at Ben Gurion University of the Negev in Israel found
that large doses of inositol””12 to 18 grams a day””helped alleviate
depression, panic disorder, and obsessive-compulsive disorder.

The study of micronutrients and mental health is known as
orthomolecular psychiatry, a term coined by two-time Nobel laureate
Linus Pauling in a controversial 1968 essay. Pauling wrote that
nutritional supplements, unlike psychotherapy or drugs, represent a
way to provide "the optimum molecular environment for the mind."
Varying the concentrations of substances normally present in the
human body, he wrote, may control mental disease even better than
conventional treatments.

Today the Society for Orthomolecular Health Medicine counts about
200 American members. One of the foremost practitioners, the
Canadian psychiatrist Abram Hoffer, claims to have successfully
treated thousands of schizophrenics with massive doses of vitamin C
and niacin. He contends the vitamins neutralize an oxidized compound
that causes hallucinations when it accumulates in the brains of
patients. Until recently, such treatments thrived on the power of
patient lore, not scientific certainty. Nutritional therapists were
generally unwilling to test their claims in well-designed controlled
studies. "Even when studies were done, they just didn't meet the
standards of rigor that would make them be taken seriously," says
Charles Popper, a Harvard University psychopharmacologist who
studies bipolar disorder.

In 1973 a task force of the American Psychiatric Association issued
a withering indictment of orthomolecular psychiatry, concluding
that "the credibility of the megavitamin proponents is low." For the
next two decades, funding for orthomolecular research was rare.
Academia turned its back on the field, and industry saw no profit in
it””vitamins and minerals can't be patented like other medicines. In
recent years, however, grants from the National Center for
Complementary and Alternative Medicine, founded in 1998, and new
discoveries in brain biochemistry have prompted researchers to take
a second look at nutritional therapies. The strongest evidence to
date involves omega-3 fatty acids, a group of compounds abundant in
fish oil of the kind Gesch gave to prisoners, as well as in the
membranes of and synapses between brain cells. In a landmark 1999
study, Harvard psychiatrist Andrew Stoll found that bipolar patients
who were given large doses of omega-3s did significantly better and
resisted relapse longer than a matched group of patients who were
given placebos.

Stoll's findings have yet to be replicated, but other researchers
have since studied omega-3s as a treatment for depression,
schizophrenia, borderline personality disorder, and attention
deficit hyperactivity disorder, or ADHD. "In every case, the data
has been overwhelmingly positive," Stoll says. Other research has
shown correlations between low levels of various nutrients””zinc,
calcium, magnesium, and B vitamins””and depression. Researchers have
found that anywhere from 15 percent to 38 percent of psychiatric
patients have reduced levels of folate. A 2000 study of older women
found that 17 percent of those who were mildly depressed and 27
percent of those suffering severe depression were short on vitamin
B12.

In an effort to winnow out confounding variables, nutritional
research has long focused on single nutrients. Yet some researchers,
like Stoll, have suggested that the effects of nutrients are
additive””that their real strength becomes apparent only in a
multinutrient formula. A formula much like the one that Tony Stephan
and David Hardy first stumbled upon in a hog barn.

After Stephan and Hardy's success, they spread word of the treatment
among fellow Mormons in southern Alberta. They began by whipping up
batches of the formula for church members suffering all sorts of
disorders, from mild depression to ADHD to schizophrenia. Then, in
early 1997, they quit their jobs and began selling the formula,
which they eventually named EMPowerplus (the EM stands
for "essential mineral"). Their company, Truehope Nutritional
Support, employs 35 people in a squat building on the edge of
Hardy's hometown, the tiny farm community of Raymond.

Stephan, 52, is stocky and energetic, with blondish-gray hair,
earnest blue eyes, and a nose that skews slightly to the right as if
it had been broken. Hardy, 55, is tall and lean, with square wire-
rimmed glasses. It's not hard to see him as the high school science
teacher he once was. The two relate the story of their supplement
with a practiced air. Both are devout Mormons who seem to believe
they've been given a mission to alleviate mental illness. Although
the supplement is not inexpensive””a month's supply costs $69.98””
Stephan and Hardy say it is expensive to manufacture, and the
business barely turns a profit.

For years, they say, they tinkered with the formula, using Autumn as
their guinea pig. "A lot of it was trial and error," Stephan
says. "There's nothing out there saying that if you're bipolar you
need 50 milligrams of zinc." The latest incarnation of the
supplement contains 36 vitamins, minerals, amino acids, and
antioxidants. Most are the same ingredients found in a typical
multivitamin but at much higher doses. For example, a daily dose of
the supplement contains a whopping 120 milligrams of vitamin E, six
times the recommended daily allowance. So far, the only side effects
appear to be nausea and diarrhea, but no one really knows the long-
term dangers of taking high vitamin and mineral doses.

News of the supplement has spread quickly through the Internet and
patient support groups. Hardy says at least 6,000 people have used
the supplement for psychiatric problems, and a few thousand more
have tried it for other central nervous system disorders such as
multiple sclerosis, Parkinson's disease, cerebral palsy, and stress.
Like many alternative therapies, the supplement has generated tales
of dramatic results, but Stephan and Hardy know that they need solid
research to prove its effects.

Several years ago, they began contacting scientists, including
Bonnie Kaplan, a research psychologist at the University of Calgary,
and Harvard's Charles Popper, inviting them to study their mixture.
The scientists had essentially the same response. "I told them to
take their snake oils somewhere else," as Kaplan later recalled to a
reporter. Popper was so leery of the pair after his first meeting
that he hid the bottle of the supplement they gave him under his
coat as he walked back to his office: "I was afraid someone was
going to see me with the stuff."

Kaplan finally agreed to meet with Hardy and Stephan in 1996.
Impressed by their sincerity, she decided to offer the formula to a
handful of patients who had not responded to conventional
treatments. Kaplan first tried the supplement on two boys with
wildly shifting moods and explosive tempers. One was so obsessed
with violent fantasies that he could not go more than 20 seconds
without thinking about guns. After he started taking the supplement,
Kaplan later wrote in a case study, his obsessions and his explosive
rage diminished. When he quit the supplements, the obsessions and
anger returned. Back on the supplements again, the symptoms
retreated.

Those results were encouraging enough that within a few months
Kaplan started a small clinical study of 11 bipolar patients who had
not been able to control their illness with conventional
medications. After six months of treatment, each of the 11 showed
improvement in both their depression and mania. Most were able to
cut down on their medications, and some quit using them altogether.

In 2000 Kaplan accompanied Hardy and Stephan to Harvard's McLean
Hospital
to talk with other scientists. Popper was skeptical,

despite Kaplan's credentials. That night, however, he got a call
from a colleague whose son had suddenly developed bipolar disorder
and was throwing violent tantrums daily. Popper reluctantly offered 
him the sample bottle of the supplement that Hardy and Stephan had
given him, figuring it couldn't hurt. He did not believe it would
help. Four days later, the father called to tell him the tantrums
were gone. "The kid wasn't even irritable," Popper recalls. "We
don't have anything in psychiatry that can do that."

Like Kaplan, Popper gradually began giving the formula to bipolar
patients who had not done well on psychotropic drugs. The supplement
not only worked for 80 percent of the patients, it also took effect
far more quickly than conventional drugs for many of them. After
testing the supplement for six months and seeing improvements in
some two dozen patients, Popper decided he had something noteworthy
enough to share with colleagues. In 2001 he and Kaplan each
published articles in The Journal of Clinical Psychiatry describing
their findings and encouraging further research. "What if some
psychiatric patients could be treated with inexpensive vitamins and
minerals rather than expensive patented pharmaceuticals?" Popper
wrote. It was a strikingly optimistic statement about a discredited
idea. "I knew going public would raise a lot of eyebrows, that I was
putting my career on the line," Popper says. "But I was convinced."

BRAIN POWER 
If preliminary studies hold true, vitamin supplements may suffice to
flip a switch in the mind, curing mental illnesses without recourse
to drugs.

One reason that orthomolecular psychiatry was treated with such
derision in the 1960s and early '70s was that biologists had only a
faint understanding of the physical effects that nutrients had on
the brain. In the past two decades, however, researchers have begun
to gain a better understanding of the brain's biochemical machinery.
Psychiatrists now know that nutrients are the brain's backstage
crew, endlessly constructing and maintaining cellular set designs,
directing players to their marks. They also play important roles in
the creation of chemical messengers thought to mediate mood, such as
serotonin, dopamine, and norepinephrine. Zinc is a particularly
versatile player, involved in more than 300 enzymatic reactions;
when zinc goes missing, a cell's DNA and its repair machinery can be
damaged.

Neuroscientist Bryan Kolb, at the Canadian Centre for Behavioural
Neuroscience in Lethbridge, Alberta, has explored how brain cells
are affected by drugs, hormones, and injury. When Stephan and Hardy
first approached him in 1997, he politely declined to start up a
study. He had little psychiatric expertise, he explained, and his
usual experimental subjects had four legs and long tails.

Two years ago, Kolb decided to take another look. In an effort to
tease out a biochemical pathway that might account for the clinical
effects that Kaplan, Popper, and others had described, he ran a
series of rat studies. First, he inflicted injuries in two parts of
infant rats' brains: the frontal lobe, which controls motor function
and the ability to plan and execute tasks, and the parietal lobe,
which influences spatial functions. Half the group then got a diet
spiked with a supplement similar to EMPowerplus and half got plain
rat chow. When Kolb put them through a series of cognitive and
spatial-ability tests, the vitamin-charged rats did markedly better
than the control group.

Kolb noticed something else about the supplement-fed rats: "They
were unbelievably calm." Lab rats usually flinch and squeal when
identification tags are stapled onto their ears, he says. "These
rats acted like nothing had happened." Kolb then autopsied the rats'
brains: The formula-fed rats had bigger brains than the chow-fed
rats. In areas near where he'd inflicted lesions, the dendrites of
the existing cells””the long, tentacled parts of neurons that conduct
electrical impulses””had sprouted new branches, each ending with
hundreds of new synapses. (In an earlier study, Kolb had found that
the amino acid choline could also stimulate dendritic growth. But
the results weren't as pronounced.)

Kolb can't say if such neural connections could alleviate  mental
illness. Schizophrenia may be associated with structural
abnormalities in the brain, but so far that's not thought to be the
case in mood disorders like depression or bipolar disorder. Whatever
the mechanism, Kolb says, he's persuaded that "the diet can clearly
alter brain function."

Of course, not everyone with a vitamin deficiency grows violent or
sinks into a clinical depression. So why might a nutritional
supplement help only some people? Kaplan has a possible explanation:
Some of us have "inborn errors of metabolism." We are born with
unusual nutritional requirements that can affect our mental
function. Mental illness appears to be partly heritable (bipolar
disorder, for one, runs in families), yet no one has discovered a
gene for the disease. Perhaps, Kaplan speculates, what's passed down
is a gene that affects the metabolic pathways influenced by various
nutrients. Some people may simply inherit a metabolism that demands
higher-than-normal amounts of vitamins and minerals. "What's optimal
for me may not be optimal for someone with a mental illness," Kaplan
said at a meeting of the American Psychiatric Association in
2003. "I've been blessed with a stable mood, and I could probably
eat a terrible diet and not have any problems. Others may need
additional supplementation."

The next research step should be a controlled randomized trial of
how bipolar patients taking supplements fare compared with those
taking a placebo. Such studies are the gold standard for testing
drugs and supplements. But Kaplan and Popper's efforts have been
stalled by controversy. The two scientists have been under attack by
a group led by Terry Polevoy, a dermatologist in Kitchener, Ontario,
who runs a Web site called HealthWatcher.net. A onetime devotee of
holistic therapies, Polevoy now crusades against alternative
treatments he considers scams. For the past four years, he and his
colleagues have accused Stephan and Hardy of irresponsibly marketing
an unproven remedy. The employees that take the company's orders
have no medical training, Polevoy points out, yet they're told to
encourage customers, many of them mentally ill, to stop using
traditional medicines and rely exclusively on the
supplement. "People have been injured by taking this stuff," Polevoy
says. In one well-publicized case, a schizophrenic man quit his
medications in order to take the supplement and wound up psychotic,
in jail, and facing assault charges.

Hardy and Stephan, in turn, accuse Polevoy of being a front man for
the pharmaceutical industry, a charge Polevoy denies. "I may go to a
few meetings a year hosted by pharmaceutical companies," Polevoy
says, "but I'm not paid."

After Kaplan and Popper published accounts of their experiences with
the formula, Polevoy charged the scientists with conducting
experimental research on patients without proper institutional
review. The allegations triggered lengthy investigations by the
scientists' academic institutions, as well as by Canadian and U.S.
health authorities. Kaplan and Popper were ultimately cleared of any
improprieties, but the ordeal left both so gun shy that they stopped
talking publicly about the supplement. (Kaplan declined to be
interviewed for this story. Neither she nor any of the other
scientists mentioned in this story have any financial ties to the
supplement.)

Both scientists have had a tough time securing government support
for their psychiatric research. EMPowerplus has yet to be approved
for sale in Canada, and Health Canada, the agency that regulates
food and drugs in that country, has sued Truehope for advertising
the product to Canadians who might wish to import it. "The
manufacturer has not provided us with scientific evidence that the
drug is safe and effective," says Jirina Vlk, a spokeswoman for the
agency. Hardy and Stephan, in turn, have sued Health Canada for
blocking shipments at the border. Health Canada initially denied
Kaplan permission to pursue a randomized study of the supplement in
100 bipolar patients, although Kaplan already had funding from the
Alberta government. That decision was reversed in 2004, after the
agency established a new division dedicated to overseeing
supplements and natural health products.

Meanwhile in the United States, Popper and Kaplan recently secured
approval from the Food and Drug Administration to conduct an even
larger clinical study of the supplement. Other scientists think this
is long overdue. "It's something that needs to be investigated,"
says L. Eugene Arnold, a psychiatrist at Ohio State University who
plans to explore the use of zinc to treat ADHD. "There's no point in
people arguing about whether it works or not without getting some
data to get the answer." Arnold is no advocate of alternative
treatments for mood disorders, but he thinks it's reasonable to
suspect that vitamins and minerals might have an effect. The
standard treatment for bipolar disorder is lithium, he points
out. "And what is that but a mineral?"

For Hardy and Stephan, the long wait for scientific validation has
been frustrating. But they are patient. "It's like any new discovery””
acceptance is slow to come," Stephan says. "But that will change. It
will come."

FISH THERAPY
Omega-3s are a family of fatty acids found in seafood and certain
plants such as flax. Researchers are interested in their therapeutic
potential for several reasons: Large population studies have shown a
correlation between rates of seafood consumption and depression.
Small studies have found patients with depression have reduced
levels of these fatty acids in their blood. A variety of small
clinical trials have also suggested that omega-3s (at doses ranging
from one to four grams) may alleviate the symptoms of depression,
schizophrenia, and bipolar disorder, as well as improve patients'
response to conventional medicines.  Some researchers speculate that
fatty acids help maintain fluidity in the cellular membranes,
allowing neural receptors to better detect incoming signals. Others,
like Harvard psychiatrist Andrew Stoll, believe that omega-3s affect
the brain in ways similar to mood-stabilizing drugs like lithium and
Depakote: They tamp down excessive signaling between cells. Stoll
says the compounds also reduce cellular inflammation””common in
people with mental disorders””stirred up by omega-6s, another family
of fatty acids. In centuries past, humans ate a great deal of wild
game, greens, and other foods rich in omega-3s. Today we eat fewer
omega-3s, while filling up on foods heavy with processed vegetable
oils, which are high in omega-6s. The change may help account for
the increased incidence of depression in the past 100 years, Stoll
says. Stoll's colleagues say that the compounds show promise but
require further research. "The problem is there's not a lot of
published evidence yet," says Harvard psychiatrist David
Mischoulon. "So it's hard to compare this modest body of evidence
against evidence for a medication like Prozac or Zoloft that has
numerous studies to back it up."      ””S.F.


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The Vitamin Cure Can common nutrients curb violent tendencies and dispel clinical depression? By Susan Freinkel Photography by Dan Winters DISCOVER Vol. 26 No. 05 | May 2005 | Biology & Medicine Mental Machinery  The brain and other complex mechanisms of the human nervous system rely on 40 or so basic nutrients to run smoothly.…
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