The
National Health Federation's Proposals for Nutrient Reference
Values
by Paul Anthony Taylor
March 31, 2004
Subject: CCNFSDU: NRV's Electronic Working Group
Dear Working Group Member,
At the recent CCNFSDU meeting in Bonn (November 2003), an
electronic Working
Group was established under the leadership of South Africa to
update the Nutrient
Reference values [Codex Guidelines on Nutrition Labeling -
CAC/GL 2-1985 (Rev.1 - 1993)].
Interested members are now invited to forward proposals for
additional or
revised NRV's for labeling purposes to the following e-mail
address before or
on 31 March 2004:
E-mail: booyza@health.gov.za
I enclose (as a Microsoft Word attachment) the National Health
Federation's
proposals for additional/revised NRVs. I would also be
grateful if you could
confirm to me that the document has been safely received and
that you have
been able to open it successfully.
Hope all is well with you.
Kind regards,
Paul Anthony Taylor
on behalf of the National Health Federation (NHF)
Proposals of the National Health Federation for
additional/revised Codex NRVs for labeling purposes
Contents
NHF Contact Details
Introduction
Vitamin A
Vitamin B1
Vitamin B2
Niacin
Pantothenic Acid
Vitamin B6
Vitamin B12
Folate
Biotin
Vitamin C
Vitamin D
Vitamin E
Vitamin K
Boron
Calcium
Copper
Chromium
Iodine
Iron
Magnesium
Manganese
Molybdenum
Selenium
Zinc
References
Introduction
The World Health Organization currently attributes one-third
of all global deaths annually (15.3 million) to cardiovascular
disease (332), and in 2000 over 6 million deaths occurred
globally from cancer (333). Moreover, estimates predict that
by 2020 the total number of cases of cancer will have
increased by 73% in the developing world and by 29% in the
developed world. (333). By 2020 it is estimated that chronic
diseases will account for almost three-quarters of all deaths
worldwide (561).
Faced with these statistics we are forced to question the
wisdom of assuming that populations are healthy merely because
they don’t suffer from classical nutritional deficiency
diseases such as scurvy, rickets, beri-beri or pellagra.
Current estimates of nutritional sufficiency, be they RDAs,
AIs, EARs or NRVs, do not set nutritional intakes with the
concept of optimum health in mind. They are simply estimates
of the amounts of nutrients that healthy populations would
require to maintain normal function and health and to avoid
nutritional deficiency diseases. This approach, in our
opinion, is highly flawed.
Given the increasing prevalence in our societies of conditions
such as cardiovascular disease, cancer, obesity, diabetes,
asthma, eczema, psoriasis, allergies, arthritis, high blood
pressure, osteoporosis and depression, we believe that by
definition our current system of nutritional values is no
longer applicable.
Moreover, the consistency of evidence in the scientific
literature clearly demonstrates that individuals who consume
nutritional supplements have a lower risk of contracting
serious disease - a position that has now been taken by two of
the world's leading medical journals.
The Journal of the American Medical Association, for example,
recently reversed its historical anti-vitamin policy by
acknowledging that "it appears prudent for all adults to take
vitamin supplements" (562). The article, authored by Robert H.
Fletcher and Kathleen M. Fairfield from the Harvard School of
Medicine, examined English-language articles about vitamins in
relation to chronic diseases published between 1966 and 2002,
and concluded that inadequate intake of several vitamins has
been linked to the development of diseases including coronary
heart disease, cancer, and osteoporosis.
Similarly, the April 9, 1998 issue of the New England Journal
of Medicine featured an article entitled "Eat Right and Take a
Multivitamin" that was based on a succession of positive
studies showing the disease-prevention benefits resulting from
the consumption of nutritional supplements (563).
We therefore consider that it would be a major step forward
for global public health if the CCNFSDU were to finally accept
and support the growing medical evidence that vitamin and
mineral supplements prevent disease, promote optimum health
and prolong lifespan.
Research has shown that there appears to be little-to-no risk
to supplement users of experiencing adverse side effects due
to excessive intakes of micronutrients (564).
We therefore propose the NRVs contained in this document as
the minimum preventative intakes necessary to prevent disease,
promote optimum health and prolong lifespan in the majority of
people.
We also strongly believe that it is the duty of the CCNFSDU to
make recommendations that advance nutritional welfare, prevent
disease, promote optimum health and prolong lifespan and that
as such a general recommendation supporting the use of
nutritional supplements would admirably fulfill all of these
criteria.
Paul Anthony Taylor
NHF Board Member & Codex Delegate
29th March 2004
Vitamin A
Note: Includes provitamin A carotenoids that are dietary
precursors of retinol. Given as retinol activity equivalents (RAEs).
1 RAE = 1 µg retinol, 12 µg beta-carotene.
Infants
0-6 mo 400µg
7-12 mo 500µg
Children
1-3 y 500µg
4-8 y 650µg
Males
9-13 y 1050µg
14-18 y 1680µg
19-30 y 1800µg
31-50 y 1800µg
50-70 y 1800µg
> 70 y 1800µg
Females
9-13 y 880µg
14-18 y 1350µg
19-30 y 1400µg
31-50 y 1400µg
50-70 y 1400µg
> 70 y 1400µg
Pregnancy
≤ 18 y 1550µg
19-30y 1600µg
31-50 y 1600µg
Lactation
≤ 18 y 1750µg
19-30y 1800µg
31-50 y 1800µg
Justification: The Helsinki Consultation in 1988 set a NRV for
vitamin A of 800 microgrammes of retinol equivalent. In
setting this figure the Consultation took into consideration
the relation between carotene and the prevention of cancer,
and stated that although this subject had not yet been
resolved from the scientific point of view, it considered that
this aspect might lead to an increase in the international
recommended daily intakes in the future when new scientific
data was available. Since 1988 however a large body of
scientific evidence has clearly demonstrated that higher
intakes of carotenes and/or preformed vitamin A are protective
against the development of a number of cancers. (1-23).
Although some research exists to suggest that large doses of
beta-carotene may possibly be capable of increasing the risk
of lung cancer in smokers, we consider that in view of the
many important health benefits to be obtained from higher
intakes of carotenes it would be irresponsible for the CCNFSDU
to recommend lower intakes for the entire population, as a
means of protecting smokers, when official WHO policy is to
substantially reduce the incidence of tobacco use. Tobacco,
not carotene, is the main cause of lung cancer in smokers.
We also consider that the case for vitamin A being linked to
birth defects has been overstated in some cases. In one study,
for example, no birth defects were reported among 120 infants
exposed to maternal intakes of vitamin A greater than 50,000
IU per day. (24). In addition, compared to the infants that
were not exposed to high maternal doses of vitamin A the
infants in this study that were exposed to high doses actually
experienced a 50% decreased risk for birth defects. In fact,
excessive dietary intake of vitamin A has been associated with
birth defects in humans in fewer than 20 reported cases over
the past 30 years. (25). Other data suggests that 30,000 IU of
vitamin A per day should be considered safe for pregnant
women. (26).
Vitamin B1
Infants
0-6 mo 3mg
7-12 mo 6mg
Children
1-3 y 8mg
4-8 y 13mg
Males
9-13 y 23mg
14-18 y 37mg
19-30 y 40mg
31-50 y 40mg
50-70 y 40mg
> 70 y 40mg
Females
9-13 y 23mg
14-18 y 37mg
19-30 y 40mg
31-50 y 40mg
50-70 y 40mg
> 70 y 40mg
Pregnancy
≤ 18 y 38mg
19-30y 41mg
31-50 y 41mg
Lactation
≤ 18 y 39mg
19-30y 42mg
31-50 y 42mg
Justification: There is now a wealth of research demonstrating
that higher intakes of thiamin can improve general health and
prevent disease. (27-49). This research also includes evidence
that currently used assays may not be adequate to assess
thiamin status, and that thiamin deficiency is under diagnosed
in life, in part because the classical clinical presentations
are uncommon.
Furthermore, given that some of this research has shown that
alcohol use, even moderate, interferes with thiamin metabolism
(more so than with any other nutrient), we consider this
increase in the NRV for thiamin to be both appropriate and
essential.
No adverse effects associated with thiamin from food or
supplements have ever been reported.
Vitamin B2
Infants
0-6 mo 3mg
7-12 mo 6mg
Children
1-3 y 8mg
4-8 y 13mg
Males
9-13 y 23mg
14-18 y 37mg
19-30 y 40mg
31-50 y 40mg
50-70 y 40mg
> 70 y 40mg
Females
9-13 y 23mg
14-18 y 37mg
19-30 y 40mg
31-50 y 40mg
50-70 y 40mg
> 70 y 40mg
Pregnancy
≤ 18 y 38mg
19-30y 41mg
31-50 y 41mg
Lactation
≤ 18 y 39mg
19-30y 42mg
31-50 y 42mg
Justification: Riboflavin has been shown to be protective
against the development of degenerative diseases (62, 68), and
studies have repeatedly demonstrated that worldwide intakes of
riboflavin are below recommended values (50, 51, 52, 55, 59,
65).
Research has also shown that supplementation of riboflavin can
improve health and wellbeing; either taken with other
nutrients (53, 54, 60, 63, 69), or alone (56, 58); and that
early detection of vitamin deficiency is difficult to diagnose
due to the fact that it often occurs without any of the
clinical signs of vitamin deficiency being present. (53).
Given that riboflavin intake has additionally been found to be
inversely associated with coronary heart and vascular disease
deaths and hospitalizations, as well as being a contributory
factor in a number of other disease conditions when intake is
insufficient (61, 64, 67), we consider this increase in the
NRV for riboflavin to be entirely appropriate. (57).
Finally, we also note that a supplement of 15mg riboflavin has
been shown to be insufficient to achieve normal biochemical
indices in pregnancy (66), and that no adverse effects
associated with riboflavin from food or supplements have been
reported.
Niacin
Includes nicotinic acid amide, nicotinic acid
(pyridine-3-carboxylic acid), and derivatives that exhibit the
biological activity of nicotinamide.
Infants
0-6 mo 15mg
7-12 mo 30mg
Children
1-3 y 40mg
4-8 y 60mg
Males
9-13 y 120mg
14-18 y 190mg
19-30 y 200mg
31-50 y 200mg
50-70 y 200mg
> 70 y 200mg
Females
9-13 y 120mg
14-18 y 190mg
19-30 y 200mg
31-50 y 200mg
50-70 y 200mg
> 70 y 200mg
Pregnancy
≤ 18 y 200mg
19-30y 210mg
31-50 y 210mg
Lactation
≤ 18 y 205mg
19-30y 215mg
31-50 y 215mg
Justification: Increased consumption of niacin has been shown
to prevent a range of diseases, illnesses and adverse health
events; including heart attacks (70), migraine headaches (71),
and cancer (72, 73). It has also been found to be effective in
the treatment of schizophrenia (74-80), arthritis and joint
disorders (81, 82), insulin-dependent diabetes (83), and
hypoglycemia (84), and has repeatedly been shown to lower
blood levels of cholesterol and triglycerides (85-93).
Pantothenic Acid
Infants
0-6 mo 15mg
7-12 mo 30mg
Children
1-3 y 40mg
4-8 y 60mg
Males
9-13 y 120mg
14-18 y 190mg
19-30 y 200mg
31-50 y 200mg
50-70 y 200mg
> 70 y 200mg
Females
9-13 y 120mg
14-18 y 190mg
19-30 y 200mg
31-50 y 200mg
50-70 y 200mg
> 70 y 200mg
Pregnancy
≤ 18 y 200mg
19-30y 210mg
31-50 y 210mg
Lactation
≤ 18 y 205mg
19-30y 215mg
31-50 y 215mg
Justification: Pantothenic acid and its natural derivatives
have been shown to prevent and alleviate arthritis (94, 95);
lower levels of cholesterol and other lipids (96-100); boost
energy and athletic ability (101); and improve immune response
(102).
Vitamin B6
Infants
0-6 mo 3mg
7-12 mo 7mg
Children
1-3 y 10mg
4-8 y 16mg
Males
9-13 y 29mg
14-18 y 47mg
19-30 y 50mg
31-50 y 50mg
50-70 y 50mg
> 70 y 50mg
Females
9-13 y 29mg
14-18 y 47mg
19-30 y 50mg
31-50 y 50mg
50-70 y 50mg
> 70 y 50mg
Pregnancy
≤ 18 y 49mg
19-30y 52mg
31-50 y 52mg
Lactation
≤ 18 y 50mg
19-30y 53mg
31-50 y 53mg
Justification: Studies in the elderly have repeatedly shown
prevalences of B6 deficiency of around 25% (103). The
prevalence of B6 deficiency, demonstrated biochemically, in
population studies in developed countries, generally ranges
from 9% in pre-school children (104), to 68% in pregnant women
on low incomes (105). Studies in adults repeatedly show
prevalences of B6 deficiency of around 25% (106).
Oral contraceptives have been shown to deplete levels of
vitamin B6 (110-114). Not surprisingly then, vitamin B6
supplements can restore normal biochemical values (115, 116)
and protect against metabolic imbalances in women taking these
drugs (117).
Vitamin B6 supplements have also been shown to boost immunity
in the elderly (107), reduce the risk of developing kidney
stones in women (108), and relieve symptoms of pre-menstrual
tension (109); as well as being effective in the treatment of
autism (118), asthma (119), sickle cell anaemia (120), and
morning sickness (121, 122). It has additionally been shown
that patients with carpal tunnel syndrome are deficient in
vitamin B6 (123), and that vitamin B6 is an effective
treatment for this disorder (124, 125). Researchers have also
demonstrated that levels of homocysteine, a risk factor for
heart disease and stroke, can be reduced by supplements of
vitamin B6, vitamin B12 and folic acid (126-129), and that
levels of vitamins B6 are inversely related to homocysteine
levels (126, 130). Levels of vitamin B6 are also inversely
related to risk of lung cancer in men. (131).
Finally, we note that vitamin B6 is considered safe during
pregnancy, and that it has been used in pregnant women without
any evidence of foetal harm (132). Furthermore, it has also
been found to have a positive effect upon pregnancy outcome
(133), and to prevent certain types of seizures in infants
(134).
Given all of the above evidence therefore, we consider this
increase in the NRV for pyridoxine to be entirely appropriate.
Vitamin B12
Infants
0-6 mo 7µg
7-12 mo 15µg
Children
1-3 y 20µg
4-8 y 30µg
Males
9-13 y 60µg
14-18 y 90µg
19-30 y 100µg
31-50 y 100µg
50-70 y 100µg
> 70 y 100µg
Females
9-13 y 60µg
14-18 y 90µg
19-30 y 100µg
31-50 y 100µg
50-70 y 100µg
> 70 y 100µg
Pregnancy
≤ 18 y 94µg
19-30y 104µg
31-50 y 104µg
Lactation
≤ 18 y 97µg
19-30y 107µg
31-50 y 107µg
Justification: A number of population groups have been shown
to have dietary intakes below the RDA for vitamin B12
(135-137), and vitamin B12 deficiency is estimated to affect
10%-15% of individuals over the age of 60 (138). Vitamin B12
deficiency becomes increasingly common with advancing age
(139), and current findings in the scientific literature
suggest that even subtle B12 deficiency is clinically
significant (140). Frank deficiencies carry many health risks,
and low serum levels of vitamin B12 are known to increase the
risk of breast cancer in women (141), as well as being
associated with a doubling of the risk of developing
Alzheimer's disease (142).
Vitamin B12, when taken with folic acid, has been shown to be
effective in the treatment of osteoarthritic hands (143), and
has been found to reduce the incidence of bronchial squamous
metaplasia, a precancerous change - even in heavy smokers
(144-145). It has also been demonstrated to be capable of
curing sciatica (146), reversing some of the effects of
chronic nitrous oxide exposure (147), and when taken with the
amino acid carnitine, has been shown to be effective in the
treatment of anorexia nervosa (148).
There is now abundant evidence that high levels of
homocysteine are associated with an increased risk of
developing cardiovascular disease (149-161), and that serum
levels of vitamin B12 are inversely related to homocysteine
levels (162-163). It has also been shown that a deficiency of
vitamin B12 can raise levels of homocysteine (164), and that
supplementation with combinations of folic acid, vitamin B6
and vitamin B12 is an effective means to reduce elevated
levels of homocysteine (165-168). Raised levels of
homocysteine have also been shown to increase the risk of
developing Alzheimer's disease (169).
Observational studies have found that as many as 30% of
patients hospitalized for depression are deficient in vitamin
B12 (170), and that vitamin B12 deficient women over the age
of 65 are twice as likely to be severely depressed as
non-deficient women (171). Indeed, there is also
epidemiological evidence that even a moderate deficiency of
vitamin B12 may lead to mental illness (172).
Supplementation of vitamin B12 has been shown to have a
significant positive effect upon memory (173), and to improve
emotional state, even in the absence of deficiency (174).
Studies have additionally shown that vitamin supplements that
include vitamin B12 are associated with better performance on
difficult visuospatial and abstraction tests (175), and that
regular use of such supplements confers some degree of
protection against vitamin B12 deficiency in older adults
(176).
Finally, researchers have also shown that vitamin B-12
dependency disorders are common and that they are neglected by
the medical profession (174), and that the cut-off point of
serum concentration should be raised, because many elderly
people with "normal" serum vitamin B12 concentrations are
metabolically deficient in cobalamin (177).
We therefore have no hesitation in recommending the above
increase in the NRV for vitamin B12.
Folate
Infants
0-6 mo 65µg
7-12 mo 120µg
Children
1-3 y 155µg
4-8 y 260µg
Males
9-13 y 465µg
14-18 y 750µg
19-30 y 800µg
31-50 y 800µg
50-70 y 800µg
> 70 y 800µg
Females
9-13 y 465µg
14-18 y 750µg
19-30 y 800µg
31-50 y 800µg
50-70 y 800µg
> 70 y 800µg
Pregnancy
≤ 18 y 780µg
19-30y 830µg
31-50 y 830µg
Lactation
≤ 18 y 815µg
19-30y 865µg
31-50 y 865µg
Justification: Many studies have shown that an inadequate
intake of folate is relatively common (178-187), and research
over the past 30 years has demonstrated a relationship between
folic acid deficiency and psychopathology (188).
Neuropsychiatric diseases secondary to folate deficiency may
include dementia, schizophrenia-like syndromes, insomnia,
irritability, forgetfulness, endogenous depression, organic
psychosis, peripheral neuropathy, myelopathy, and restless
legs syndrome (189). Low serum folate levels are also known to
be associated with a doubling of the risk of developing
Alzheimer's disease (142).
Higher levels of folate however have been shown to be related
to a lower incidence of nuclear lens opacities, which are
associated with the development of cataracts (193).
Data from the Nurses' Health Study conducted at the Harvard
Medical School found that long-term supplementation with folic
acid reduces the risk of colon cancer in women by 75% (190).
Indeed, there is an inverse relationship between the intake of
folate and the risk of developing various esophageal and
gastric cancers (191), and folic acid is known to be effective
in the treatment of atrophic gastritis, where it prevents or
reverses precancerous lesions (192). Furthermore, folic acid
taken with vitamin B12 has been found to be effective in the
treatment of osteoarthritic hands (143), and in the reduction
of the incidence of bronchial squamous metaplasia (a
precancerous change) - even in heavy smokers (144-145).
Folic acid supplements have also been shown to reduce blood
pressure in smokers (194), and research has established that
supplementing the diet with vitamins C, E, B6 and folate is
conducive to the prevention of cardiovascular disease (195).
In this respect there is now abundant evidence that high
levels of homocysteine are associated with an increased risk
of developing conditions such as cardiovascular disease
(149-161) and Alzheimer's disease (169), and studies have
shown that supplementation with combinations of folic acid,
vitamin B6 and vitamin B12 is an effective means to reduce
elevated levels of homocysteine (165-168).
High levels of homocysteine accompanied by low levels of
folate are also known to be risk factors for heart attack
(197). This link has been further established through research
showing that folic acid supplements can reduce levels of
homocysteine (198) and hence protect against heart attacks
(199). As such it is noteworthy that children with a family
history of CVD have been found to have lower intakes of folate,
lower serum folate levels, and higher levels of homocysteine
(196), and that supplements of folic acid, vitamin B6 and
vitamin B12 have even been shown to reduce the progression of
atherosclerosis in hyperhomocysteinemic renal-transplant
recipients (200).
Scientific evidence has now clearly demonstrated that women
given folic acid supplements during pregnancy have a lower
incidence of delivering babies with neural tube birth defects
(201-203), and researchers have therefore emphasised the
importance of all fertile women, regardless or not of whether
they are intending to become pregnant, taking daily
multivitamins that contain 400µg (0.4 mg) of folic acid (204).
Folic acid-containing multivitamins have additionally been
shown to reduce the risk of gestational hypertension (205).
It is now known that in the elderly even moderate folate
depletion will only respond to an intake of folate in excess
of the RDA (206). Researchers have also shown that folic acid
supplements are more effective than increased dietary folate
intake in elevating serum folate levels (207). Indeed, the use
of nutritional supplements is particularly beneficial in
promoting adequate intakes of folate in women aged 18-50 years
(208), and research has made it clear that people who do not
take folic acid supplements are at increased risk for
functional folate deficiency (209).
Given that research has already shown that the current RDA for
folate is insufficient to attain optimal homocysteine levels
(210), and that micronutrients both prevent cancer and delay
aging (211), there can now be little doubt that the Helsinki
Consultation’s recommendation to reduce the NRV for folate
from 400µg to 200µg was a step in the wrong direction.
Biotin
Infants
0-6 mo 60µg
7-12 mo 120µg
Children
1-3 y 155µg
4-8 y 260µg
Males
9-13 y 465µg
14-18 y 750µg
19-30 y 800µg
31-50 y 800µg
50-70 y 800µg
> 70 y 800µg
Females
9-13 y 465µg
14-18 y 750µg
19-30 y 800µg
31-50 y 800µg
50-70 y 800µg
> 70 y 800µg
Pregnancy
≤ 18 y 780µg
19-30y 830µg
31-50 y 830µg
Lactation
≤ 18 y 810µg
19-30y 860µg
31-50 y 860µg
Justification: There is good evidence that
biotin deficiency is by no means uncommon (212-216). Biotin is
essential for numerous biochemical, dermatological and
neurological processes, and long-term auditory and visual
complications can result from a deficiency in this nutrient
(217, 218). Biotin deficiency has also been found to cause mitochondrial decay with oxidant leakage leading to
accelerated aging and neural decay (219). Biotin has
furthermore been shown to improve glucose metabolism
(220-223), and research suggests that biotin supplements may
be particularly useful in the prevention of diabetes (224).
High doses of biotin may also synergize with chromium
picolinate to enable a definitive nutritional therapy for type
II diabetes, and may likewise be useful in the prevention and
management of gestational diabetes, as well as being an aid to
glycemic control in type I patients. (225). Indeed, drugs such
as metformin and troglitazone, which are expensive and require
regular physician monitoring to avoid potentially dangerous
side effects, would appear to be less practical options from
cost-effectiveness, convenience and safety standpoints, given
the fact that the population at risk for diabetes is huge.
(226). Finally, biotin supplements have also been found to
effect a marked improvement in patients suffering from severe
diabetic peripheral neuropathy (227), and have been shown to
significantly increase the growth rate and strength of hair in
children (228). Worldwide, the number of cases of diabetes is
estimated to be around 150 million, and is expected to double
by 2025 (229). Because of the wealth of research demonstrating
the ability of biotin supplements to both prevent diabetes and
improve glucose metabolism we have no hesitation in
recommending the above NRVs.
Vitamin C
Infants
0-6 mo 200mg
7-12 mo 400mg
Children
1-3 y
600mg
4-8 y 1000mg
Males
9-13 y 1750mg
14-18 y 2800mg
19-30 y
3000mg
31-50 y 3000mg
50-70 y 3000mg
> 70 y 3000mg
Females
9-13 y 1750mg
14-18 y 2800mg
19-30 y 3000mg
31-50 y 3000mg
50-70 y 3000mg
> 70 y 3000mg
Pregnancy
≤ 18 y 2900mg
19-30y
3100mg
31-50 y 3100mg
Lactation
≤ 18 y 3000mg
19-30y 3200mg
31-50 y 3200mg
Justification: Studies have shown that several population
groups have an inadequate intake of vitamin C, and that
deficiencies of ascorbic acid are far more prevalent than is
commonly believed (230-241). Moreover, patients suffering from
dementia (242), epilepsy (243), preeclampsia (244, 245),
gallbladder disease (246), schizophrenia (247, 248), coronary
artery disease (249-253), cerebral vascular disease (254),
esophageal, stomach and colorectal cancers (255, 256) and
gastric cancer (257), have all been found to have
significantly lower levels of vitamin C than are found in
normal healthy people.
Similarly, the risk of stroke has been shown to increase
significantly with a decreased intake of vitamin C (258), and
low levels of ascorbic acid are implicated in the development
of gastric cancer (259-261), periodontal disease (262), and
cardiovascular disease (263). A high intake of ascorbic acid,
on the other hand, has been found to be protective against the
development of gastric cancer (264-269, 292-296), as well as
cancers of the esophagus (270), uterus (290), oral cavity,
stomach, pancreas, cervix, rectum, lung (291), breast (291,
298, 299), ovaries (310), and others (271). In this respect it
is interesting to note that megadoses of vitamin C and other
nutrients have been shown to significantly reduce the
recurrence of tumours in patients with bladder cancer (297),
and that male smokers with a high intake of vitamin C have
been shown to have a lower risk of cancer than male smokers
with a lower intake of vitamin C (300).
Hospital patients with low levels of ascorbic acid have a
greater frequency of postoperative complications, and
administering ascorbic acid until blood levels returned to
normal has been proven to prevent postoperative complications
(327). Other researchers have demonstrated that a mixture of
vitamins C, E and A also dramatically reduces the
postoperative complication rate (328).
People with the highest levels of vitamin C have also been
found to have a significantly lower incidence of nuclear
opacities. In fact, it has been found that the longer the
duration that vitamin C supplements are taken for the lower is
the prevalence of nuclear opacities. This has led researchers
to conclude that vitamin C plays a strong role in preventing
nuclear opacities (272). Other studies recommend the use of
vitamin C and other antioxidant supplements in the prevention
of age-related cataract and macular degeneration (273), and
research also shows that that ascorbic acid can protect the
cornea from ultraviolet radiation (274).
Research has shown that a high dietary intake of vitamin C and
vitamin E may lower the risk of Alzheimer disease (329). Other
researchers have confirmed this, and have demonstrated that
long-term supplement users of vitamin E with vitamin C have
significantly better mental performance than do people who
have never used vitamin E or vitamin C supplements (331), and
that vitamins C and E may prevent dementia and improve
cognitive functioning in later life (330).
Studies have also confirmed that vitamin C has a protective
effect against the development of coronary heart disease (275,
276), and that vitamin C is beneficial in preventing the
advancement of arteriosclerosis in heart transplant patients
(277). Indeed, researchers have shown that human
cardiovascular disease is the direct consequence of the
inability of man to synthesize ascorbate in combination with
insufficient intake of ascorbate in the modern diet. Since
ascorbate deficiency is the common cause of human CVD,
ascorbate resupplementation is the universal treatment for
this disease (278). As such, the therapeutic use of vitamin C
and other nutrients may well pave the way towards a new
therapeutic goal, namely, the noninvasive reversal of existing
cardiovascular disease with nutritional supplements (279). In
that respect it is now increasingly clear that vitamin C
should be used in the treatment of coronary arterial disease
patients, and those with heart attacks, strokes, or
hypertension (301).
A daily dose of 2700 mg of Vitamin C, when taken with other
nutrients, has been shown to halt the progression of early
coronary atherosclerosis (280), and other researchers have
similarly found that the combination of vitamin C and vitamin
E can slow the advancement of atherosclerosis (281).
Furthermore, a review of studies of vitamins A, C and E and
cardiovascular disease found significant evidence to support
the supplementation of these vitamins to lower the risk of
death from this illness, and concluded that diabetics, smokers
and those with hypertension would all benefit from taking
supplemental vitamin C (282). As such, it is now clear that
the progression of early stages of coronary calcifications can
be stopped or limited by the synergistic effect of vitamins
and essential nutrients (283, 289), and that supplementing the
diet with nutrients including vitamins C, E, B6 and folate is
conducive to the prevention of cardiovascular disease (284).
In this respect it is also interesting to note that some
researchers particularly recommend dietary supplementation of
vitamin C and E in Northern Europe, where cardiovascular
disease is most prevalent (285).
Deaths from stomach cancer and cardiovascular disease and
cerebrovascular disease are all associated with low levels of
vitamin C (286); in fact it has been demonstrated that
mortality for all causes of death decreases strongly with an
increased intake of supplemental vitamin C (287). A study of
8,453 Americans’ serum ascorbic acid (SAA) levels and
mortality rates from disease, for example, found that those
with a normal to high level of SAA had a 21%-25% lower risk of
dying from cardiovascular disease, and that they had a 25%-29%
decrease in risk of mortality from all causes compared to
those with low levels of SAA (288).
Vitamin C supplements have also been shown to improve the
body’s ability to metabolize glucose and lipids and as such
are seen as being beneficial to those with Type II diabetes
(302). Similarly, people with higher levels of vitamin C have
been found to have a lower incidence and risk of hyperglycemia
(303).
Critically ill surgery patients have been shown to be
significantly less likely to experience organ failure, spend
less time using mechanical ventilation and have shorter times
in intensive care units when they are given supplements of
vitamin C and vitamin E (304).
Vitamin C supplements have been shown to be an effective
treatment for hypertension, both in non-diabetics (305-308),
and in diabetics (309), and have been found to reduce muscle
soreness and improve muscle function after exercise (317,
318).
Research has also demonstrated the ability of higher doses of
vitamin C to delay bone loss (311), and to increase bone
density (312). Similarly, an increased intake of vitamins C
and E has been shown to reduce the risk of hip fractures
(313).
Studies have also found that the duration and severity of
colds can be decreased by an increased intake of vitamin C
(314, 315), and that doses of vitamin C between 500-2000mg
improve antioxidant protection (316).
Some researchers have argued for higher intakes of vitamin C
to be recommended for populations chronically exposed to air
pollutants (such as ozone), cigarette smoking, or those doing
vigorous exercise (319). Other studies have made similar
recommendations for people who are exposed to passive smoking
(320, 321). Indeed, it has been shown that high doses of
vitamin C can reduce or eliminate the negative effect that
smoking has on blood flow (322), and that vitamin C
supplements can protect against the cardiovascular problems
caused by cigarette smoke inhalation (323). In this respect it
is also interesting to note that vitamin C supplements have
been shown to significantly reduce cholesterol, LDL-C and
triglycerides, as well as increase serum HDL (324).
Researchers also recommend that people who are smokers,
diabetics, pregnant, users of antibiotics, people who ingest
alcohol, and users of contraceptives all need to supplement
with vitamin C. (325). Indeed, vitamin C is depleted in women
who use oral contraceptives, which may result in cardiac
problems and thrombosis. (326). Since vitamin supplements are
routine for pregnancy, they should also be routine for the
pseudopregnancy of oral contraception (326).
Finally, we note that the World Health Organization currently
attributes one-third of all global deaths annually (15.3
million) to cardiovascular disease (332), and that in 2000
over 6 million deaths occurred from cancer (333). Moreover,
estimates predict that by 2020 the total number of cases of
cancer will have increased by 73% in the developing world and
by 29% in the developed world. (333). Given therefore the
proven safety and efficacy of ascorbic acid in the prevention
and treatment of both cardiovascular disease and cancer, we
have no hesitation in recommending the above NRVs for this
nutrient.
Vitamin D
Note: 1µg calciferol = 40 IU vitamin D.
Infants
0-6 mo 5µg
7-12 mo 5µg
Children 1-3 y 5µg
4-8 y 6.5µg
Males 9-13 y 12µg
14-18 y 18µg
19-30 y 20µg
31-50 y 20µg
50-70
y 20µg
> 70 y 20µg
Females
9-13 y 12µg
14-18 y 18µg
19-30 y
20µg
31-50 y 20µg
50-70 y 20µg
> 70 y 20µg
Pregnancy
≤ 18 y
20µg
19-30y 20µg
31-50 y 20µg
Lactation
≤ 18 y 20µg
19-30y
20µg
31-50 y 20µg
Justification:
Nowadays, severe deficiency of vitamin D is not a common
finding in most developed countries. However, the prevalence
of vitamin D insufficiency is relatively high and it can
contribute to the lowering of bone mass in osteoporosis risk
populations (334). In this respect it is important to note
that Vitamin D deficiency can occur without any symptoms, and
that if symptoms are present it indicates severe deficiency
(349). Moreover, serum calcium and phosphorus values do not
often predict the existence of deficiency (349).
A decrease in bone mineral density is the most important cause
of fracture (335). Among other factors, Calcium and vitamin D
deficiencies are important risk factors for a decrease in bone
mineral density, and can consequently induce osteoporosis
(335). In this respect it is interesting to note that the high
prevalence of vitamin D deficiency in healthy elderly people
in southern European countries increases the risk of
osteoporotic fractures in these populations to levels above
those anticipated for the general elderly population of the
European community (335). As such, the ageing of the European
population will double the number of osteoporotic fractures
over the next 50 years unless adequate preventative measures
are undertaken (335).
Research assessing the cost implications for a preventive
treatment strategy for institutionalised elderly women found
that the incidence of hip and other fractures was reduced by
vitamin D and calcium supplements, and concluded that such
strategies are cost saving (336). The doses given in this
study were 1200 mg/day calcium and 20µg (800 IU) daily of
vitamin D, and the data used in the research was collected
from studies conduced in seven European countries (336).
Other research concurs that a daily dose of 20µg (800 IU) of
vitamin D (or the equivalent 2500µg/100,000 IU given three
times per year) reduces the frequency of both falls (337) and
fractures (338-340). Moreover, research has shown that severe
vitamin D deficiency is present in virtually all elderly
institutionalized subjects, and that as such, routine vitamin
D supplementation is warranted for such people (341).
Studies also suggest that a daily supplement of 10µg (400 IU)
is helpful in maintaining an adequate concentration of vitamin
D in infants (342), and that vitamin D supplementation during
infancy is associated with higher bone mineral mass in
prepubertal girls (343).
Research has also shown that most cases of colon cancer may be
prevented with an intake of vitamin D in the range of 20µg
(800 IU) per day, and epidemiological data suggest that such
an intake may additionally be associated with enhanced
survival rates among breast cancer cases (344). Other evidence
from diverse areas of study - epidemiologic, molecular,
genetic, cellular, animal models, and clinical trials -
suggests that vitamin D may be an effective preventive agent
against prostate cancer (345).
Dietary supplementation of vitamin D is also associated with
reduced risk of Type-1 diabetes, and children who take a 20µg
(2000 IU) dose of vitamin D daily have been shown to have a
lower risk of developing the disease than children who do not
(346).
Women with the highest vitamin D intake from supplements
(10µg/400 IU or more per day) have been shown to be 40 percent
less likely to develop multiple sclerosis than those women who
do not use supplements (347). Similarly, women who consume
vitamin D in both supplement and food form have also been
shown to have a lower risk of developing multiple sclerosis;
whereas women who derive their intake of this vitamin from
food only do not experience a reduced risk of developing the
disease (347). In addition, patients already suffering from
multiple sclerosis who are given supplements of vitamin D,
calcium and magnesium have been shown to have a decreased rate
of relapse (348).
Research has also shown that vitamin D deficiency exists in
patients with tuberculosis, and that it is possibly a cause
rather than an effect of this disease (349). Given the fact
therefore that the incidence of this disease is currently
increasing in many countries, there exists an urgent need for
effective, affordable preventative measures to be instigated
at the earliest opportunity.
Finally, we are of the opinion that the alleged dangers of
vitamin D supplements have been exaggerated in many cases, as
single doses ranging from 200,000 units to over 500,000 units
have been given to infants both orally and by injection
without any ill effects. (350). Moreover, the weight of
evidence shows that the currently accepted, no observed
adverse effect limit of 2,000 IU per day is too low by at
least 5-fold (351). One hour of total-body sun exposure easily
provides the equivalent of 10,000 IU of vitamin D, for example
(351); clearly, many people get this on a regular basis
without experiencing toxicity symptoms. Doses of 15000µg
(600,000 IU) of vitamin D have also been given to pregnant
women in the 7th and 8th months of pregnancy without evidence
of harm (352).
Vitamin E
Infants
0-6 mo 30 IU
7-12 mo 60 IU
Children
1-3 y 80 IU
4-8 y
130 IU
Males
9-13 y 230 IU
14-18 y 370 IU
19-30 y 400 IU
31-50
y 400 IU
50-70 y 400 IU
> 70 y 400 IU
Females
9-13 y 230 IU
14-18 y 370 IU
19-30 y 400 IU
31-50 y 400 IU
50-70 y 400 IU
>
70 y 400 IU
Pregnancy
≤ 18 y 385 IU
19-30y 415 IU
31-50 y 415
IU
Lactation
≤ 18 y 400 IU
19-30y 430 IU
31-50 y 430 IU
Justification: The World Health Organization currently
attributes one-third of all global deaths annually (15.3
million) to cardiovascular disease (332), and patients with
coronary artery disease have been shown to have significantly
lower blood levels of vitamin E than normal healthy people.
(249).
Studies have demonstrated that vitamin E supplements are
effective in the treatment of cardiovascular disease
(353-355), and that the combination of vitamin E and vitamin C
can slow the advancement of atherosclerosis (281).
Furthermore, a review of studies of vitamins A, C and E and
cardiovascular disease found significant evidence to support
the supplementation of these vitamins to lower the risk of
death from this illness (282). As such, it is now clear that
the progression of early stages of coronary calcifications can
be stopped or limited by the synergistic effect of vitamins
and essential nutrients (283, 289), and that supplementing the
diet with nutrients including vitamins E, C, B6 and folate is
conducive to the prevention of cardiovascular disease (284).
In this respect it is also interesting to note that some
researchers particularly recommend dietary supplementation of
vitamin E and C in Northern Europe, where cardiovascular
disease is most prevalent (285).
Vitamin E therapy has also been shown to reduce arterial
blockage in patients suffering from intermittent claudication
(356, 357), and recent research has indicated that it
normalizes high blood pressure (358-360). Vitamin E also
promotes collateral circulation; consequently offering great
benefits to diabetes patients (361).
A recent study looked at patients with colon cancer who
received a daily dose of 750 mg of vitamin E during a period
of 2 weeks. The researchers found that supplementation with
high doses of dietary vitamin E produced a significant
improvement in the immune functions of these patients, all of
whom had advanced cancer. It is especially notable that this
improvement was achieved in only two weeks (362).
Other research suggests that vitamin E supplementation also
improves immune function in healthy elderly people (366, 367).
Research has additionally shown that a high dietary intake of
vitamin E and vitamin C may lower the risk of Alzheimer
disease (329). Other researchers have confirmed this, and have
demonstrated that long-term supplement users of vitamin E with
vitamin C have significantly better mental performance than do
people who have never used vitamin E or vitamin C supplements
(331), and that vitamins E and C may prevent dementia and
improve cognitive functioning in later life (330). Similarly,
a Columbia University study reported that the progression of
Alzheimer's disease was significantly slowed in patients
taking high daily doses (2,000 IU) of vitamin E for two years
(363).
In another study, 400 IU of vitamin E per day given to
epileptic children for several months reduced the frequency of
seizures in most of them by over 60 percent, whilst half of
them had a 90 to 100 percent reduction in seizures. This study
is also notable for the fact that the researchers specifically
stated that the children suffered no adverse side effects from
the vitamin E treatment (364). Similarly, preterm infants
given 100 mg of vitamin E per kilogram body weight (as a
preventative treatment for incubator oxygen retina damage - a
major cause of retrolental fibroplasia and subsequent
blindness in premature infants) suffer no detrimental side
effects from such therapy. (365).
It is also notable that a statistical analysis of published
clinical results showed as early as 1940 that vitamin E
supplements reduce the rate of recurrent miscarriage (368).
An increased intake of vitamins E and C has been found to
reduce the risk of hip fractures (313), and researchers have
also demonstrated that a mixture of vitamins E, C and A
dramatically reduces the postoperative complication rate
(328). Similarly, critically ill surgery patients have been
shown to be significantly less likely to experience organ
failure, spend less time using mechanical ventilation and have
shorter times in intensive care units when they are given
supplements of vitamin E and vitamin C (304).
Finally, research has shown that healthy centenarians have
high levels of both vitamin E and vitamin A, and that this
seems to be important in guaranteeing their extreme longevity
(369).
We also note that the 2000 report by the Institute of Medicine
of the National Academy of Sciences acknowledges that 1,000 mg
(1,500 IU) vitamin E is a "tolerable upper intake level . . .
that is likely to pose no risk of adverse health effects for
almost all individuals in the general population."
Vitamin K
Infants
0-6 mo 45µg
7-12 mo 90µg
Children
1-3 y 120µg
4-8 y
190µg
Males
9-13 y 350µg
14-18 y 560µg
19-30 y 600µg
31-50 y
600µg
50-70 y 600µg
> 70 y 600µg
Females
9-13 y 350µg
14-18 y
560µg
19-30 y 600µg
31-50 y 600µg
50-70 y 600µg
> 70 y 600µg
Pregnancy
14-18 y 580µg
19-30 y 620µg
31-50 y 620µg
Lactation
14-18 y 605µg
19-30 y 645µg
31-50 y 645µg
Justification: Research using healthy adults aged 19-36 years
who were given vitamin K supplements has shown that a daily
phylloquinone intake of approximately 1000µg is required to
maximally gamma-carboxylate circulating osteocalcin (370), and
that a diet low in vitamin K1 can result in a functional
subclinical deficiency of vitamin K (decreased urinary gamma-carboxyglutamic
acid excretion) without affecting blood coagulation (371).
Current estimates suggest that the dietary intake of vitamin K
is in the range 124-375 µg /d in a European population (372).
Studies have repeatedly shown that higher intakes of vitamin K
reduce the risk of hip fracture (373, 374) and that low
intakes may increase the risk of hip fracture in women (375).
This data supports the case for a reassessment of the vitamin
K requirements that are based on both blood coagulation and
bone health (375).
Low dietary vitamin K intake is also associated with low bone
mineral density in women (376), and evidence from
observational studies and first intervention trials indicate
that vitamin K intakes much higher than the current
recommendations improve both biochemical markers of bone
formation and bone density (377). In deed, the mechanistic
data as well as the observational data and the results of the
first controlled clinical trials in humans point to a
beneficial effect of additional intakes of vitamin K in bone
health (377).
Supplements of vitamin K (containing 45mg of menatetrenone)
have been shown to promote bone formation in postmenopausal
women when taken for a period of 48 weeks (378), and therapy
combining vitamin K(2) and D(3) has been shown to be useful
for increasing vertebral bone mass in postmenopausal women
(379). Similarly, research findings indicate that the combined
administration of vitamin D3 and vitamin K2 appears to be
useful in increasing the bone mineral density of the lumbar
spine in postmenopausal women with osteoporosis (380), and
that vitamin K (as menatetrenone) may be beneficial in the
prevention of bone loss in patients with anorexia nervosa
(381).
Vitamin K (as menatetrenone) has also been shown to reduce the
risk of hip fracture in elderly female Parkinson's disease
patients (382). Significant reduction in bone mineral density
occurs in patients with Parkinson's disease, resulting in an
increasing risk of hip fracture, especially in elderly women.
(382).
Research also suggests that it would be prudent to consider
routine vitamin K supplementation in patients with cystic
fibrosis, severe noncholestatic and cholestatic liver disease,
major small-bowel resection, and pancreatic insufficiency or
lung disease necessitating frequent use of antibiotics (383).
Patients with Crohn's disease have also been found to have low
serum levels of vitamin K, and as such are at particular risk
of osteoporosis (384).
Studies have demonstrated that oral vitamin K is as effective
as injectable Vitamin K in newborns, and researchers are now
recommending its usage to reduce the complications and costs
of parenteral therapy (385). Other data has confirmed the
effectiveness of oral vitamin K given to newborns in reducing
infant mortality and morbidity from bleeding disorders such as
intracranial hemorrhage (386). Indeed, additional research
suggests that supplementation of infants with vitamin K is
highly advisable, and that increments of vitamin K during
pregnancy and lactation should also be recommended (387). In
this respect it is interesting to note that maternal vitamin K
supplementation can maintain the vitamin K status of infants
throughout the late neonatal period and prevent an onset of
vitamin K-deficient hemorrhage (388).
Finally, research has also shown that low dietary vitamin K
intake is associated with an increased risk of aortic
calcification (389), and that vitamin K may play an important
role in the acute insulin response in glucose tolerance (390).
Boron
Based upon the knowledge that we have at this time, we
consider that the science suggests an optimal intake of
1.5-3mg for men and women aged 18 years and above, and that
dietary boron is sufficiently important to be considered
essential in human beings.
Justification: The daily intake of boron in humans has been
estimated to range from 0.3-41 mg. The wide range is due to
the variation of the analytical methods used and differences
in the soil content of boron (464).
Dietary boron influences the activity of many metabolic
enzymes, as well as the metabolism of steroid hormones and
several micronutrients, including calcium, magnesium, and
vitamin D (465).
Research shows that a boron supplement of 3 mg/day markedly
reduces the urinary excretion of calcium and magnesium in
post-menopausal women (466).
Because boron deprivation causes changes similar to those seen
in women with postmenopausal osteoporosis, this element is
apparently needed for optimal calcium metabolism and is thus
needed to prevent the excessive bone loss which often occurs
in postmenopausal women and older men (467).
The elevation of endogenous estrogen as a result of
supplementation suggests a protective role for boron in
atherosclerosis (468).
When contrasted with the high boron intake, low dietary boron
results in significantly poorer performance on tasks
emphasizing manual dexterity; eye-hand coordination;
attention; perception; encoding and short-term memory; and
long-term memory. Data indicates that boron may play a role in
human brain function and cognitive performance, and provides
additional evidence that boron is an essential nutrient for
humans (469).
Evidence suggests boron is a safe and effective treatment for
some forms of arthritis. Epidemiologic evidence shows that in
areas of the world where boron intakes usually are 1.0 mg or
less/day the estimated incidence of arthritis ranges from 20
to 70%, whereas in areas of the world where boron intakes are
usually 3 to 10 mg, the estimated incidence of arthritis
ranges from 0 to 10%. Experimental evidence from a
double-blind placebo-boron supplementation trial with 20
subjects with osteoarthritis showed a significant favorable
response to a 6mg boron/day supplement, in that 50% of
subjects receiving the supplement improved compared to only
10% receiving the placebo. This data indicates that boron is
an essential nutrient for healthy bones and joints (470).
Finally, men who ingest the greatest amount of boron have been
shown to be 64% less likely to develop prostate cancer
compared to men who consumed the least amount of boron (471).
Calcium
Infants
0-6 mo 210mg
7-12 mo 270mg
Children
1-3 y 500mg
4-8 y 800mg
Males
9-13 y 1300mg
14-18 y 1300mg
19-30 y 1000mg
31-50 y 1000mg
50-70 y 1200mg
> 70 y 1200mg
Females
9-13 y 1300mg
14-18 y 1300mg
19-30 y 1000mg
31-50 y 1000mg
50-70 y 1200mg
> 70 y 1200mg
Pregnancy
≤ 18 y 1300mg
19-30y 1000mg
31-50 y 1000mg
Lactation
≤ 18 y 1300mg
19-30y 1000mg
31-50 y 1000mg
Justification: The above figures are the current US NRVs for
calcium (391), and we broadly concur with both the US
supporting data and with other research which suggests that
the daily consumption of calcium in the diet should,
optimally, be at least 1200 mg/day (392).
Copper
Infants
0-6 mo 200µg
7-12 mo 290µg
Children
1-3 y 390µg
4-8 y
645µg
Males
9-13 y 1160µg
14-18 y 1870µg
19-30 y 2000µg
31-50
y 2000µg
50-70 y 2000µg
> 70 y 2000µg
Females
9-13 y 970µg
14-18 y 1570µg
19-30 y 1680µg
31-50 y 1680µg
50-70 y 1680µg
>
70 y 1680µg
Pregnancy
≤ 18 y 1670µg
19-30y 1780µg
31-50 y
1780µg
Lactation
≤ 18 y 1770µg
19-30y 1880µg
31-50 y 1880µg
Justification: Several national food surveys in the United
States have revealed marginally to moderately low contents of
copper in the typical American diet (393), and the dietary
intake of copper has been shown to be below the recommended
daily allowance in several different population groups.
(394-396).
Metabolic balance studies have demonstrated that daily copper
losses are approximately 1.3mg/day (397). In order to remain
in copper balance, the average adult male must consume a diet
that contains at least 2mg copper/day. (397). However, some
research suggests that up to eighty-one per cent of people
consume less than 2mg of copper in their daily diets (398),
and that a marginal deficiency of this trace element exists in
up to 62% of people suffering from hypertension (399). In this
respect it is interesting to note that supplementation with
5mg of copper per day has been shown to decrease both systolic
and diastolic blood pressure in patients with mild stable
hypertension (399).
Research has shown that the recovery from mild copper
depletion may require more aggressive intervention than 2mg
per day of copper taken for 35 days (400), and a review of
studies of experimental copper deprivation conducted in adult
humans indicated that 2.6mg of copper per day taken for
periods of up to 42 days is similarly sufficient for recovery
from copper deprivation (401). Studies from animal models and
in human volunteers have permitted to construct a provisional
continuum of acceptable intakes of copper that would avoid
copper deficiency and/or toxicity: acceptable intakes may vary
between 10 and 50µg/kg body weight (402).
Men and women fed diets close to 1mg of copper per day,
amounts quite frequent in the United States, responded with
reversible, potentially harmful changes in blood pressure
control, cholesterol and glucose metabolism, and
electrocardiograms (403). Copper deficiency is also known to
impair cell-mediated immunity (408).
Numerous anatomical, chemical and physiological similarities
between animals deficient in copper and people with ischemic
heart disease have been noticed (403, 406), and a correlation
has been established between low intake of copper and
prevalence of ischemic heart disease, dyslipoproteinemia,
arterial hypertension and excessive body mass (404). Dietary
copper deficiency may also impair cardiovascular health by
contributing to enhancement of inflammation, anemia and
reduced blood clotting (405).
Indeed, some researchers believe that more features of the
etiology, pathogenesis, and pathophysiology of ischemic heart
disease can be explained in terms of copper deficiency than
can be explained by any other environmental insult (406). It
is interesting to note therefore that people with ischemic
heart disease have been shown to have decreased cardiac and
leucocyte copper and decreased activities of some
copper-dependent enzymes (407).
Chromium
Infants
0-6 mo 15µg
7-12 mo 30µg
Children
1-3 y 40µg
4-8 y 65µg
Males
9-13 y 115µg
14-18 y 190µg
19-30 y 200µg
31-50 y 200µg
50-70 y 200µg
> 70 y 200µg
Females
9-13 y 115µg
14-18 y 190µg
19-30 y 200µg
31-50 y 200µg
50-70 y 200µg
> 70 y 200µg
Pregnancy
≤ 18 y 210µg
19-30y 210µg
31-50 y 210µg
Lactation
≤ 18 y 215µg
19-30y 215µg
31-50 y 215µg
Justification: Normal dietary intake of chromium for humans is
suboptimal, and most diets contain less than 60% of the
minimum suggested intake of 50µg (409).
Suboptimal dietary intake of chromium is associated with an
increase in risk factors associated with diabetes and
cardiovascular diseases (410), and produces signs and symptoms
similar to those seen in these diseases (411).
Supplemental chromium is associated with a reduction in the
risk factors for maturity-onset diabetes and cardiovascular
diseases (412). Supplemental chromium given to people with
impaired glucose tolerance or diabetes leads to improved blood
glucose, insulin, and lipid variables (409).
Diabetics are frequently found to be low in chromium (413).
Research has also demonstrated that plasma chromium levels are
significantly lower in patients with coronary artery disease
(423), and rheumatoid arthritis (424).
A daily supplement containing 200µg has been shown in some
patients to be capable of reducing their requirements for
insulin, sulfonylurea or metformin (414). Other research
similarly confirms the beneficial effects of chromium
supplements in individuals with diabetes (415-418). However,
it is important to note that the beneficial effects of
chromium in individuals with diabetes are generally only
observed at levels higher than the upper limit of the
Estimated Safe and Adequate Daily Dietary Intake (419). 200µg
per day of supplemental chromium is adequate to improve
glucose variables of those who are mildly glucose intolerant,
whereas people with more overt impairments in glucose
tolerance and diabetes usually require more than 200µg per day
(420).
Chromium supplementation of normal adult men, as well as
diabetics, has been reported to increase high density
lipoprotein cholesterol and decrease triglycerides and total
cholesterol (421). Indeed, some researchers consider that the
beneficial effects of chromium repletion are now so well
established and the trivalent form is so free of toxicity that
it should now be used in clinical medicine for the benefit of
those with some forms of diabetes and its complications and
those suffering from atherosclerosis (422).
Chromium has also been shown to have antidepressant effects in
patients with atypical depression (425), and has been found to
be capable of increasing lean body mass in obese patients
(426). Niacin-bound chromium supplements at a daily dose of
600µg have been demonstrated to cause overweight women on a
modest dietary and exercise regimen to lose a significant
amount of fat compared to placebo (427).
Finally, most recent evidence strongly supports the conclusion
that there is little fear of toxic reactions from chromium
consumption, and that supplementation may be useful to
ameliorate many of the manifestations of ageing (411). In this
respect, we note that the 350-fold difference between the
acceptable daily intake and the calculated reference dose for
humans of 70µg per day seems without precedent with respect to
other nutritional minerals, and that the beneficial effects of
chromium on serum glucose and lipids and insulin resistance
occur even in the healthy (428).
Iodine
Infants
0-6 mo 110µg
7-12 mo 130µg
Children
1-3 y 90µg
4-8 y 90µg
Males
9-13 y 120µg
14-18 y 150µg
19-30 y 150µg
31-50 y 150µg
50-70 y 150µg
> 70 y 150µg
Females
9-13 y 120µg
14-18 y 150µg
19-30 y 150µg
31-50 y 150µg
50-70 y 150µg
> 70 y 150µg
Pregnancy
≤ 18 y 220µg
19-30y 220µg
31-50 y 220µg
Lactation
≤ 18 y 290µg
19-30y 290µg
31-50 y 290µg
Justification: The above figures are the current US NRVs for
iodine (429), and the FAO/WHO Helsinki Consultation similarly
set a figure of 150µg for Iodine when it met in 1988. We
currently see no reason to alter these figures.
Iron
Infants
0-6 mo 0.27mg
7-12 mo 11mg
Children
1-3 y 7mg
4-8 y 10mg
Males
9-13 y 8mg
14-18 y 11mg
19-30 y 8mg
31-50 y 8mg
50-70 y 8mg
> 70 y 8mg
Females
9-13 y 8mg
14-18 y 15mg
19-30 y 18mg
31-50 y 18mg
50-70 y 8mg
> 70 y 8mg
Pregnancy
≤ 18 y 27mg
19-30y 27mg
31-50 y 27mg
Lactation
≤ 18 y 10mg
19-30y 9mg
31-50 y 9mg
Justification: The above figures are the current US NRVs for
iron (430), and we broadly concur with the US supporting data.
Magnesium
Infants
0-6 mo 40mg
7-12 mo 75mg
Children
1-3 y 95mg
4-8 y 160mg
Males
9-13 y 290mg
14-18 y 480mg
19-30 y 500mg
31-50 y 500mg
50-70 y 500mg
> 70 y 500mg
Females
9-13 y 290mg
14-18 y 480mg
19-30 y 500mg
31-50 y 500mg
50-70 y 500mg
> 70 y 500mg
Pregnancy
≤ 18 y 500mg
19-30y 520mg
31-50 y 520mg
Lactation
≤ 18 y 520mg
19-30y 540mg
31-50 y 540mg
Justification: Research shows that dietary magnesium
consumption has progressively declined over the past century
from an average intake of 475-500mg in the period 1900-1908 to
an average intake of 175-225mg in the period 1990-2002 (431).
As such it is hardly surprising that suboptimal intakes of
magnesium and outright magnesium deficiencies are now
commonplace in many population groups (435-452). Indeed, a
large segment of the U.S. population may have a chronic latent
magnesium deficiency that has been linked to atherosclerosis,
myocardial infarction, hypertension, cancer, kidney stones,
premenstrual syndrome, and psychiatric disorders (453). In
this respect it should be noted that although serum levels are
commonly used to assess magnesium deficiency, red cells and
leucocytes can be still deficient despite normal serum values
(454).
Magnesium deficiency produces abnormal cardiac rhythms that
can cause sudden death from a heart attack (432, 433), and
optimal levels of magnesium are strongly related to a lower
risk of heart disease (434). Moreover, magnesium deficiency is
commonplace in patients suffering from congestive heart
failure (438), and a correlation between low magnesium
consumption and the prevalence of the ischemic heart disease
has been observed (451, 449). Further supporting evidence for
the role of magnesium in protecting the heart can be drawn
from the fact that magnesium infusions in patients with acute
myocardial infarction have been shown to reduce the incidences
of arrhythmias, death and the size of infarction (444).
In addition, serum magnesium levels are also known to be
inversely associated with the risk of hypertension (448), and
research has demonstrated that hypomagnesemia detected at the
time of admission to hospital of acutely ill medical patients
is associated with an increased mortality rate for both ward
and intensive care unit patients (455).
Erythrocyte magnesium levels in patients with premenstrual
tension syndrome have been shown to be significantly lower
than those of the normal population (456), and as such it is
believed that magnesium deficiency may also play a role in the
etiology of this syndrome (457). Similarly, the biochemical
signs of chronic magnesium deficiency are also known to be
present in patients suffering from osteoporosis (459-461) and
diabetes (462, 463).
Finally, we note that a 100 mg/day higher magnesium intake has
been shown to be associated with better lung function and a
reduced risk of airway hyper-reactivity and wheezing (458),
and that a number of age-related neurodegenerative diseases
have also been linked with various types of magnesium
depletion (446).
Given that the World Health Organization currently attributes
one-third of all global deaths annually (15.3 million) to
cardiovascular disease (332) we have no hesitation in
recommending the above NRVs for magnesium.
Manganese
Infants
0-6 mo 0.4mg
7-12 mo 0.9mg
Children
1-3 y 1.2mg
4-8 y
1.9mg
Males
9-13 y 3.5mg
14-18 y 5.6mg
19-30 y 6.0mg
31-50 y
6.0mg
50-70 y 6.0mg
> 70 y 6.0mg
Females
9-13 y 2.9mg
14-18 y
4.7mg
19-30 y 5.0mg
31-50 y 5.0mg
50-70 y 5.0mg
> 70 y 5.0mg
Pregnancy
≤ 18 y 4.9mg
19-30y 5.2mg
31-50 y 5.2mg
Lactation
≤
18 y 5.1mg
19-30y 5.4mg
31-50 y 5.4mg
Justification: Patients suffering from osteoporosis have been
found to have low blood levels of manganese (472, 473), and
studies suggest that manganese supplements, either alone or in
combination with other minerals, may both prevent fractures
and halt bone loss (474, 475).
People with diabetes may also have low blood levels of
manganese (476), and research suggests that manganese
deficiency can contribute to glucose intolerance and that this
may be reversed by supplementation (477).
Similarly, manganese deficiency may also aggravate Meniere’s
disease (481).
Research has also demonstrated that manganese supplements can
both prevent and reverse the development of Tardive Dyskinesia
(478-480).
Manganese is often low in refined and processed foods (482,
483). As such therefore, people whose diets consist primarily
of these types of foods may consequently have a low manganese
intake.
Finally, an increased manganese intake may be especially
important whenever iron is supplemented, because iron can
reduce the absorption of manganese and cause lower body levels
of it (484).
Molybdenum
Infants
0-6 mo 10µg
7-12 mo 20µg
Children
1-3 y 30µg
4-8 y 50µg
Males
9-13 y 90µg
14-18 y 140µg
19-30 y 150µg
31-50 y 150µg
50-70 y 150µg
> 70 y 150µg
Females
9-13 y 70µg
14-18 y 100µg
19-30 y 125µg
31-50 y 125µg
50-70 y 125µg
> 70 y 125µg
Pregnancy
≤ 18 y 105µg
19-30y 130µg
31-50 y 130µg
Lactation
≤ 18 y 110µg
19-30y 135µg
31-50 y 135µg
Justification: The average diet in Western countries contains
up to 500µg of molybdenum daily (485, 486).
Molybdenum levels in soil have been shown to be substantially
lower in areas with the highest incidence of esophageal cancer
(486, 487), and research suggests that molybdenum deficiency
is associated with oesophageal cancer (486, 488).
Moreover, molybdenum also has an inhibitory effect upon
gastrointestinal carcinogenesis, and research has demonstrated
inverse correlations between molybdenum levels and female
mortality from cancers of the esophagus and rectum (489).
Asthma symptoms are known to be triggered in some people by
ingestion of sulfites, and molybdenum has been shown to aid in
the detoxification of sulfites (490).
Trials have used molybdenum supplements in amounts of 500µg
per day in the treatment of such conditions (491).
Molybdenum has also been shown to be useful in the treatment
of children whose teeth have become stained through the
ingestion of fluorine (492).
Finally, we note that molybdenum is accepted as an essential
element and that it has a relatively low toxicity (485).
Selenium
Infants
0-6 mo 15µg
7-12 mo 30µg
Children
1-3 y 40µg
4-8 y 65µg
Males
9-13 y 115µg
14-18 y 190µg
19-30 y 200µg
31-50 y 200µg
50-70 y 200µg
> 70 y 200µg
Females
9-13 y 115µg
14-18 y 190µg
19-30 y 200µg
31-50 y 200µg
50-70 y 200µg
> 70 y 200µg
Pregnancy
≤ 18 y 210µg
19-30y 210µg
31-50 y 210µg
Lactation
≤ 18 y 215µg
19-30y 215µg
31-50 y 215µg
Justification: Selenium intake has been shown to be inadequate
in many countries, and selenium deficiency is now relatively
commonplace (493-501).
Research has demonstrated an inverse relationship between
serum selenium levels and the incidence of cancer (502), and
mounting evidence reveals that selenium has both
anticarcinogenic and antitumorigenic properties (503).
Studies have also shown that the lower the soil levels of
selenium are in a region the higher will be the prevalence of
cancer in that region (504-506). In this respect it is
interesting to note that researchers have measured the
selenium content of the soil across the whole of the United
States and found that it varies widely; the highest levels
being found in the soil of South Dakota, and the lowest levels
being found in Ohio. Analysis of this research showed that
Rapid City, South Dakota, had the lowest overall cancer
mortality rate in the whole of the United States, whilst the
death rate from cancer in Ohio was almost twice that of South
Dakota (507-510). Additional research has confirmed these
results and extended them to almost thirty countries;
definitively showing that the lower the intake of selenium the
higher was the incidence of leukaemia and cancers of the large
intestine, rectum, prostate, breast, ovary, lung, pancreas,
skin and bladder (511). As such, the mythical “healthy diet”
is clearly insufficient to prevent the development of cancer
in areas where selenium is deficient in the soil.
Selenium supplements have been shown to reduce both the
incidence of cancer and mortality resulting from it (512-516).
Research has clearly shown, for example, that 200µg of
supplemental selenium a day can reduce overall cancer
mortality by 50% in humans compared to a placebo group not
receiving supplemental selenium (517).
Research has also demonstrated an inverse relationship between
serum selenium levels and the incidence of cardiovascular
disease (502). Similarly, there is a significant, inverse
correlation between plasma levels of selenium and severity of
coronary atherosclerosis (518), and the serum selenium
concentration of patients with acute myocardial infarction has
been shown to be significantly lower than that of healthy
people (519, 520). Indeed, low serum levels of selenium are
associated with an increased risk of death from acute coronary
heart disease and a higher risk of both fatal and nonfatal
myocardial infarction (521). These findings are corroborated
by separate research which shows a lower life expectancy and
an elevated mortality from endemic and chronic diseases for
people living in areas where the soil is deficient in selenium
(534).
It has also been demonstrated that in the United States there
is an inverse relationship between the quantity of selenium in
the soil and mortality from AIDS (522). In this respect it is
interesting to note that a selenium supplement of 200µg has
been shown to markedly decrease the hospital admission rates
of patients infected with HIV, decreasing the cost for
hospitalization by 58% (523).
Patients with systemic inflammatory response syndrome (SIRS)
have been found to have low selenium levels (524), as have
patients suffering from chronic pancreatitis (525), and
muscular dystrophy (526). Research also suggests that the
incidence of goiter is related to low serum levels of selenium
(529).
Selenium supplements have been found to improve immune
function in corticoid-dependent asthmatics (527), and in
patients on haemodialysis (528). When taken with supplements
of vitamin E, selenium supplements, have also been shown to
produce an improvement of sperm motility and semen quality
(530, 531).
Finally, it has been shown that the lower the level of
selenium in the diet the more subjects report feelings of
anxiety, depression, and tiredness. A 100µg supplement of
selenium however has been shown to elevate mood and in
particular, decrease anxiety (532, 533).
Zinc
Infants
0-6 mo 2mg
7-12 mo 4mg
Children
1-3 y 6mg
4-8 y 10mg
Males
9-13 y 17mg
14-18 y 28mg
19-30 y 30mg
31-50 y 30mg
50-70 y 30mg
> 70 y 30mg
Females
9-13 y 14mg
14-18 y 23mg
19-30 y 25mg
31-50 y 25mg
50-70 y 25mg
> 70 y 25mg
Pregnancy
≤ 18 y 24mg
19-30y 26mg
31-50 y 26mg
Lactation
≤ 18 y 25mg
19-30y 27mg
31-50 y 27mg
Justification: An insufficient intake of zinc and/or zinc
deficiency has been shown to be relatively common (393-395,
535-540), and a high serum copper concentration in the
presence of low serum zinc is known to be associated with an
increased mortality from all cardiovascular diseases and from
coronary heart disease in particular (548).
Similarly, children who suffer from allergies are at risk of
zinc deficiency (553), and patients suffering from Parkinson's
disease have been found to be functionally deficient in this
nutrient (550).
Levels of zinc have also been shown to be significantly
reduced in type-2 diabetes mellitus (541) and it has been
established that zinc supplementation is helpful in achieving
better glycemic control and improvement in the severity of
peripheral neuropathy in diabetic patients (542).
Researchers have also demonstrated inverse correlations
between blood pressure and serum levels of zinc (545), and
that inadequate intakes of zinc are associated with an
increased risk of bone fractures in middle-aged and elderly
men (549).
Serum levels of zinc are frequently diminished in human
immunodeficiency virus (HIV) infection, (543, 544), and
research has shown that low levels of plasma zinc predict a
3-fold increase in HIV-related mortality, whereas
normalization has been associated with significantly slower
disease progression and a decrease in the rate of
opportunistic infections (544).
It has also been shown that in patients with chronic liver
disease the hepatic zinc concentration decreases as the
severity of liver damage increases. Researchers have therefore
suggested that zinc supplementation may improve hepatic
encephalopathy by increasing the efficiency of the urea cycle
(546). Indeed, zinc supplementation has also been found to
improve glucose disposal in patients with cirrhosis (547).
Zinc supplements can have beneficial effects on the immune
response in elderly people (556), and can decrease the
incidence of infection and increase the survival rate
following infection (557). Similarly, treatment of the common
cold with zinc gluconate lozenges has been shown to result in
a significant reduction in duration of symptoms (560).
In patients suffering from macular degeneration zinc
supplements can reduce the visual loss associated with this
disease (558).
Research also suggests that zinc inhibits human prostatic
carcinoma cell growth (559).
People suffering from tinnitus have been shown to have lower
levels of zinc than people who do not have tinnitus, and zinc
supplements are known to be effective in decreasing the
severity of this condition (551, 552).
Finally, we note that boys suffering from acne have been shown
to have significantly lower serum levels of zinc than healthy
subjects of the same age (554), and that researchers have
demonstrated that zinc supplements are an effective treatment
for this common adolescent condition (555).
REFERENCES
1. Cancer Epidemiol Biomarkers Prev. 2003 Aug;12(8):713-20.
Premenopausal intakes of vitamins A, C, and E, folate, and
carotenoids, and risk of breast cancer. Cho E, Spiegelman D,
Hunter DJ, Chen WY, Zhang SM, Colditz GA, Willett WC.
2. Br J Cancer. 2003 May 6;88(9):1381-7. Dietary intakes of
vitamins A, C, and E and risk of melanoma in two cohorts of
women. Feskanich D, Willett WC, Hunter DJ, Colditz GA.
3. J Biol Regul Homeost Agents. 2003 Jan-Mar;17(1):92-7.
Retinoids in chemoprevention of cancer. Verma AK.
4. Plant Foods Hum Nutr. 2002 Fall;57(3-4):319-41.
Palm oil: biochemical, physiological, nutritional,
hematological, and toxicological aspects: a review. Edem DO.
5. Asian Pac J Cancer Prev. 2001 Jul-Sep;2(3):215-224. A Study
of Various Sociodemographic Factors and Plasma Vitamin Levels
in Oral and Pharyngeal Cancer in Gujarat, India. Patel PS,
Raval GN, Patel DD, Sainger RN, Shah MH, Shah JS, Patel MM,
Dutta SJ, Patel BP.
6. Cancer Sci. 2003 Jan;94(1):57-63. Serum carotenoids and
mortality from lung cancer: a case-control study nested in the
Japan Collaborative Cohort (JACC) study. Ito Y, Wakai K,
Suzuki K, Tamakoshi A, Seki N, Ando M, Nishino Y, Kondo T,
Watanabe Y, Ozasa K, Ohno Y; JACC Study Group.
7. Curr Drug Metab. 2003 Feb;4(1):1-10. Retinoic acid
metabolism and mechanism of action: a review. Marill J, Idres
N, Capron CC, Nguyen E, Chabot GG.
8. J Am Coll Nutr. 1995 Oct;14(5):419-27. Epidemiologic
studies of antioxidants and cancer in humans. Flagg EW, Coates
RJ, Greenberg RS.
9. Bibl Nutr Dieta. 1995;(52):75-91. Cardiovascular disease
and vitamins. Concurrent correction of 'suboptimal' plasma
antioxidant levels may, as important part of 'optimal'
nutrition, help to prevent early stages of cardiovascular
disease and cancer, respectively. Gey KF.
10. Cancer Causes Control. 2001 Feb;12(2):163-72. Dietary
patterns, nutrient intake and gastric cancer in a high-risk
area of Italy. Palli D, Russo A, Decarli A.
11. Soz Praventivmed. 1989;34(2):75-7. Vitamins and cancer:
results of a Basel study Stahelin HB.
12. Am J Epidemiol. 1991 Apr 15;133(8):766-75. Plasma
antioxidant vitamins and subsequent cancer mortality in the
12-year follow-up of the prospective Basel Study. Stahelin HB,
Gey KF, Eichholzer M, Ludin E, Bernasconi F, Thurneysen J,
Brubacher G.
13. Ital J Gastroenterol. 1991 Sep-Oct;23(7):429-35. Gastric
cancer in Italy. Cipriani F, Buiatti E, Palli D.
14. EXS. 1992;62:398-410. Inverse correlation between
essential antioxidants in plasma and subsequent risk to
develop cancer, ischemic heart disease and stroke
respectively: 12-year follow-up of the Prospective Basel
Study. Eichholzer M, Stahelin HB, Gey KF.
15. Int J Cancer. 1994 Mar 1;56(5):650-4. Serum micronutrients
in relation to pre-cancerous gastric lesions. Zhang L, Blot WJ,
You WC, Chang YS, Liu XQ, Kneller RW, Zhao L, Liu WD, Li JY,
Jin ML, et al.
16. Am J Epidemiol. 1994 Mar 1;139(5):466-73. Nutritional
factors and gastric cancer in Spain. Gonzalez CA, Riboli E,
Badosa J, Batiste E, Cardona T, Pita S, Sanz JM, Torrent M,
Agudo A.
17. Int J Cancer. 1994 Jun 1;57(5):638-44. Nutrients and
gastric cancer risk. A population-based case-control study in
Sweden. Hansson LE, Nyren O, Bergstrom R, Wolk A, Lindgren A,
Baron J, Adami HO.
18. Int J Cancer. 1995 Mar 16;60(6):748-52. Attributable risks
for stomach cancer in northern Italy. La Vecchia C, D'Avanzo
B, Negri E, Decarli A, Benichou J.
19. Zhonghua Yu Fang Yi Xue Za Zhi. 1995 Jul;29(4):198-201.
Relationship between serum micronutrients and precancerous
gastric lesions Zhang L, Zhao L, Ma J.
20. Int J Cancer. 1996 Apr 10;66(2):145-50 Prediction of male
cancer mortality by plasma levels of interacting vitamins:
17-year follow-up of the prospective Basel study. Eichholzer
M, Stahelin HB, Gey KF, Ludin E, Bernasconi F.
21. Cancer Lett. 1999 Feb 8;136(1):89-93
Serum antioxidative vitamin levels and lipid peroxidation in
gastric carcinoma patients. Choi MA, Kim BS, Yu R.
22. . Int J Cancer. 1998 Nov 9;78(4):415-20. Nutrient intake
patterns and gastric cancer risk: a case-control study in
Belgium. Kaaks R, Tuyns AJ, Haelterman M, Riboli E.
23. J Nutr. 2002 Apr;132(4):756-61. A dietary oxidative
balance score of vitamin C, beta-carotene and iron intakes and
mortality risk in male smoking Belgians. Van Hoydonck PG,
Temme EH, Schouten EG.
24. Mastroiacovo P, Mazzone T, Addis A, Elephant E, Carlier P,
Vial T, Garbis H, Robert E, Bonati M, Ornoy A, Finardi A,
Schaffer C, Caramelli L, Rodriguez-Pinilla E, Clementi M. High
vitamin A intake in early pregnancy and major malformations: a
multicenter prospective controlled study. Teratology. 1999
Jan;59(1):7-11.
25. Biesalski HK. Comparative assessment of the toxicology of
vitamin A and retinoids in man. Toxicology 1989;57:117–61).
26. Wiegand UW, Hartmann S, Hummler H. Safety of vitamin A:
recent results. Int J Vitam Nutr Res 1998;68:411–6 [review].
27. Lonsdale D. The Nutritionist's Guide lo the Clinical Use
of Vitamin B-1. Tacoma, WA: Life Sciences Press: 44-77.
28. Cheraskin E, Ringsdorf WM, Medford FH, Hicks BS. The
"ideal" daily vitamin B1 intake. J Oral Med 1978;33:77-79.
29. Am J Clin Nutr, 2002, vol.75, 616-58, 377. High-dose
vitamin therapy stimulates variant enzymes with decreased
coenzyme binding affinity (increased K-m): relevance to
genetic disease and polymorphisms. Ames BN et al.
30. Cheraskin E, Ringsdorf WM. How much carbohydrate should we
eat? Am Lab 1974;6:31-35.
31. Nutr Rev. 2002 Sep;60(9):277-80. Acute versus marginal
deficiencies of nutrients. Carpenter KJ. USA
32. Neurochem Int. 2002 May;40(6):493-504. Interactions of
oxidative stress with thiamine homeostasis promote
neurodegeneration. Gibson GE, Zhang H.
33. Am J Ophthalmol. 2001 Jul;132(1):19-26. Use of vitamin
supplements and cataract: the Blue Mountains Eye Study.
Kuzniarz M, Mitchell P, Cumming RG, Flood VM.
34. Br J Nutr. 2001 Jun;85(6):741-8. Vitamin B intake and
status in healthy Havanan men, 2 years after the Cuban
neuropathy epidemic. Arnaud J, Fleites-Mestre P, Chassagne M,
Verdura T, Garcia Garcia I, Hernandez-Fernandez T, Gautier H,
Favier A, Perez-Cristia R, Barnouin J.
35. Behav Brain Res. 2001 Mar 15;119(2):167-77. Aging
potentiates the acute and chronic neurological symptoms of
pyrithiamine-induced thiamine deficiency in the rodent. Pitkin
SR, Savage LM.
36. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2000
Feb;35(1):19-27.
Alcohol intake and nutrition. Itokawa Y.
37. Public Health Nutr. 1999 Sep;2(3A):403-9. The effects of
nutrients on mood. Benton D, Donohoe RT.
38. Wei Sheng Yan Jiu. 1997 Mar;26(2):122-5. Relationship
between dietary nutrients intakes and human prostate cancer Du
S, Shi L, Zhang H, He S.
39. Psychopharmacology (Berl). 1997 Jan;129(1):66-71.
Thiamine supplementation mood and cognitive functioning.
Benton D, Griffiths R, Haller J. UK
40. Z Ernahrungswiss. 1996 Sep;35(3):266-72. Can megadoses of
thiamine prevent ethanol-induced damages of rat hippocampal
CA1 pyramidal neurones? Wenisch S, Steinmetz T, Fortmann B,
Leiser R, Bitsch I.
41. Metab Brain Dis. 1996 Mar;11(1):95-106. Effects of
thiamine supplementation on exercise-induced fatigue. Suzuki
M, Itokawa Y. Japan
42. J Neurochem. 1996 Jan;66(1):250-8. Thiamine, thiamine
phosphates, and their metabolizing enzymes in human brain.
Bettendorff L, Mastrogiacomo F, Kish SJ, Grisar T.
43. J Med Assoc Thai. 1993 Oct;76 Suppl 2:138-45. Effects of
multivitamin supplementation for improvement of thiamin,
riboflavin, and retinol nutrition in pediatric patients.
Angkatavanich J, Suthutvoravut U, Panijpan B, Tontisirin K.
44. J Epidemiol Community Health. 1991 Jun;45(2):148-51.
Relation between diet composition and coronary heart disease
risk factors. Porrini M, Simonetti P, Testolin G, Roggi C,
Laddomada MS, Tenconi MT.
45. Int J Cancer. 1998 Nov 9;78(4):415-20. Nutrient intake
patterns and gastric cancer risk: a case-control study in
Belgium. Kaaks R, Tuyns AJ, Haelterman M, Riboli E.
46. Med Hypotheses. 2000 Jul;55(1):88-90. Thiamine
supplementation to prevent induction of low birth weight by
conventional therapy for gestational diabetes mellitus. Bakker
SJ, ter Maaten JC, Gans RO.
47. Am J Clin Nutr. 2000 Aug;72(2 Suppl):598S-606S. Effect of
physical activity on thiamine, riboflavin, and vitamin B-6
requirements. Manore MM.
48. Age Ageing. 2000 Mar;29(2):111-6. Comment in: Age Ageing.
2000 Mar;29(2):99-101. Is thiamine deficiency in elderly
people related to age or co-morbidity? Wilkinson TJ, Hanger
HC, George PM, Sainsbury R.
49. Arch Neurol. 1995 Nov;52(11):1081-6. Plasma and red blood
cell thiamine deficiency in patients with dementia of the
Alzheimer's type. Gold M, Chen MF, Johnson K.
50. J Nutr Health Aging. 2003;7(2):121-8. Assessment of
antioxidant nutrient intake of a population of southern U.S.
African-american and caucasian women of various ages when
compared to dietary reference intakes. Lewis SM, Mayhugh MA,
Freni SC, Thorn B, Cardoso S, Buffington C, Jairaj K, Feuers
RJ.
51. Pol Merkuriusz Lek. 2002 Dec;13(78):490-6. Dietary intake
elderly subjects in rural and urban area in Poland, Rychlik E.
52. Eur J Clin Nutr. 2002 Nov;56(11):1119-25. Diet and
nutritional status of rural adolescents in India. Venkaiah K,
Damayanti K, Nayak MU, Vijayaraghavan K.
53. J Med Assoc Thai. 1993 Oct;76 Suppl 2:138-45. Effects of
multivitamin supplementation for improvement of thiamin,
riboflavin, and retinol nutrition in pediatric patients.
Angkatavanich J, Suthutvoravut U, Panijpan B, Tontisirin K.
54. Vopr Pitan. 2001;70(1):12-4. Effects of biologically
active supplements on the antioxidant and vitamin status of
patients with hypertension and ischemic heart disease.
Tutel'ian VA, Pogozheva AV, Rumiantseva OI, Akol'zina SE,
Lysikova SL, Kodentsova VM, Mal'tsev GIu.
55. J Am Diet Assoc. 1995 Dec;95(12):1409-13. High-risk
nutrient intakes among low-income Mexican women in Chicago,
Illinois. Ballew C, Sugerman SB.
56. Biochem Biophys Res Commun. 1995 Jul 6;212(1):35-40.
Myocardial flavin reductase and riboflavin: a potential role
in decreasing reoxygenation injury. Mack CP, Hultquist DE,
Shlafer M.
57. J Am Coll Nutr. 1995 Feb;14(1):71-9. The important role of
modifiable dietary and behavioral characteristics in the
causation and prevention of coronary heart disease
hospitalization and mortality: the prospective NHANES I
follow-up study. Gartside PS, Glueck CJ.
58. Nutr Rev. 1993 May;51(5):149-50. Riboflavin can protect
tissue from oxidative injury. Christensen HN.
59. J Epidemiol Community Health. 1991 Jun;45(2):148-51.
Relation between diet composition and coronary heart disease
risk factors. Porrini M, Simonetti P, Testolin G, Roggi C,
Laddomada MS, Tenconi MT.
60. Atherosclerosis. 1989 Jan;75(1):1-6. Reduction of plasma
lipid and homocysteine levels by pyridoxine, folate, cobalamin,
choline, riboflavin, and troxerutin in atherosclerosis.
Olszewski AJ, Szostak WB, Bialkowska M, Rudnicki S, McCully
KS.
61. Ann Rheum Dis. 1996 Nov;55(11):837-40. Glutathione
reductase activity, riboflavin status, and disease activity in
rheumatoid arthritis. Mulherin DM, Thurnham DI, Situnayake RD.
62. Int J Epidemiol. 1998 Oct;27(5):845-52. Nutritional
factors in the aetiology of multiple sclerosis: a case-control
study in Montreal, Canada. Ghadirian P, Jain M, Ducic S,
Shatenstein B, Morisset R.
63. Epilepsy Res. 2002 Oct;51(3):237-47. The effect of
B-vitamins on hyperhomocysteinemia in patients on
antiepileptic drugs. Apeland T, Mansoor MA, Pentieva K,
McNulty H, Seljeflot I, Strandjord RE.
64. Eur J Clin Nutr. 1988 Apr;42(4):277-83. Riboflavin
deficiency and severity of malaria. Das BS, Das DB, Satpathy
RN, Patnaik JK, Bose TK.
65. Food consumption and dietary adequacy according to income
in 1,200 families, Manaus, Amazonas, Brazil, 1973-1974.
Shrimpton R.
66. Hum Nutr Clin Nutr. 1983 Dec;37(6):427-32. Efficacy of a
riboflavin supplement given at fortnightly intervals to
pregnant and lactating women in rural Gambia. Bates CJ,
Flewitt A, Prentice AM, Lamb WH, Whitehead RG.
67. Am J Clin Nutr. 2003 Jun;77(6):1352-60. Riboflavin
(vitamin B-2) and health. Powers HJ.
68. Arch Ophthalmol. 2001 Jul;119(7):1009-19. Long-term
nutrient intake and early age-related nuclear lens opacities.
Jacques PF, Chylack LT Jr, Hankinson SE, Khu PM, Rogers G,
Friend J, Tung W, Wolfe JK, Padhye N, Willett WC, Taylor A.
69. Neuropsychobiology. 1995;32(2):98-105. Vitamin
supplementation for 1 year improves mood. Benton D, Haller J,
Fordy J.
70. Canner PL et al. Fifteen year mortality in coronary drug
project patients: Long term benefit with niacin. Journal of
the American College of Cardiology. 8:1245-1255, 1986.
71. Velling DA, Dodick DW, Muir JJ. Sustained-release niacin
for prevention of migraine headache. Mayo Clin Proc. 2003
Jun;78(6):770-1.
72. Negri E, Franceschi S, Bosetti C, et al. Selected
micronutrients and oral and pharyngeal cancer. Int J Cancer.
2000;86(1):122-127.
73. Franceschi S, Bidoli E, Negri E, et al. Role of
macronutrients, vitamins and minerals in the aetiology of
squamous-cell carcinoma of the oesophagus. Int J Cancer.
2000;86(5):626-631.
74. Hawkins D. Orthomolecular psychiatry: Treatment of
schizophrenia. In: Hawkins D and Pauling L (eds.).
Orthomolecular psychiatry. San Francisco: WH Freeman and
Company, pp. 667-668, 1973.
76. Hoffer, A., Osmond, H., Callbeck, J.M., and Kahan, I.
(1957) Treatment of schizophrenia with nicotinic acid and
nicotinamide. Journal of Clinical Experimental Psychopathology
18:131-158.
77. Hoffer, Abram (1962) Niacin Therapy in Psychiatry.
Springfield, IL: Charles S. Thomas.
78. Hoffer, Abram and Osmond, Humphrey Treatment of
schizophrenia with nicotinic acid: a ten-year follow-up. Acta
Psychiatr Scand 40:171-189. 1964.
79. Hoffer, Abram. Use of ascorbic acid with niacin in
schizophrenia. Canadian Medical Journal, November 6. 1971.
80. Osmond, Humphrey and Hoffer, Abram (1962) Massive niacin
treatment in schizophrenia: review of a nine-year study.
Lancet 1:316-319.
81. Hoffer A. Treatment of arthritis by nicotinic acid and
nicotinamide. Can. Med. Assoc. J. 81:235, 1959.
82. Kaufman W. Niacinamide therapy for joint mobility:
Therapeutic reversal of a common clinical manifestation of the
‘normal’ ageing process. Conn. St. Med. J. 81:235, 1959.
83. Vogue P et al. Nicotinamide may extend remission phase in
insulin-dependent diabetes. Lancet. 1:619, 1987.
84. Shansky. Vitamin B3 in the alleviation of Hypoglycemia.
Drug and Cosmetic Industry. Oct. 1981.
85. Carlson LA, Hamsten A and Asplund A. Pronounced lowering
of serum levels of lipoprotein Lp(a) in hyperlipidemic
subjects treated with nicotinic acid. Journal of Internal
Medicine. 226:271-276, 1989.
86. Luria MH. Effect of low-dose niacin on high density
lipoprotein cholesterol and total cholesterol/high density
lipoprotein cholesterol ratio. Archives of Internal Medicine.
148:2493-2495, 1988.
87. Yovos JG et al. Effects of nicotinic acid therapy on
plasma lipoproteins and very low density lipoprotein
apoprotein C subspecies in hyperlipoproteinerria. Journal of
Clinical Endocrinology and Metabolism. 54:1210-1215, 1982.
88. Charman et al. Nicotinic acid in the treatment of
hypercholesterolemia. J. Angiology. Jan. 1973.
89. The effect of Nicotinic Acid on the Plasma Free Fatty
Acids. Acta Medica Scandinavica 172 fasc. 6, 1962.
90. Miettinen et al. Acta Med. Scand. 186:247-253, 1969.
91. Altschul R, Hoffer A, Stephen JD. Influence of nicotinic
acid on serum cholesterol in man. Archives of Biochemistry and
Biophysics. 54:558-559, 1955.
92. Guraker A, Hoeg JM, Kostner G, Papadopoulos NM, Brewer HB
Jr. Levels of lipoprotein Lp(a) decline with neomycin and
niacin treatment. Atherosclerosis. 57:293-301, 1985.
93. Lavie CJ. Marked benefit with sustained-release niacin
therapy in patients with isolated very low levels of
high-density lipoprotein cholesterol and coronary artery
disease. The American Journal of Cardiology. 69:1083-1085,
1992.
94. Barton-Wright EC and Elliott WA. The pantothenic acid
metabolism of rheumatoid arthritis. Lancet. 2:862-863, 1963.
95. General Practitioner Research Group. Calcium pantothenate
in arthritic conditions. Practitioner. 224:208-211, 1980.
96. Gaddi A, Descovich GC, Noseda G, et al. Controlled
evaluation of pantethine, a natural hypolipidemic compound, in
patients with different forms of hyperlipoproteinemia.
Atherosclerosis. 1984;50(1):73-83.
97. Coronel F, Tornero F, Torrente J, et al. Treatment of
hyperlipemia in diabetic patients on dialysis with a
physiological substance. Am J Nephrol. 1991;11(1):32-36.
98. Avogaro P, Bon GB, Fusello M. Effect of pantethine on
lipids, lipoproteins and apolipoproteins in man. Current
Therapeutic Research. 33:488-493, 1983.
99. Galeone F, Scalabrino A, Giuntoli F, Birindelli A,
Panigada G, Rossi, Saba P. The lipid-lowering effect of
pantethine in hyperlipidemic patients: A clinical
investigation. Current Therapeutic Research. 34:383-390, 1983.
100. Miccoli R, Marchetti P, Sampietro T, Benzi L, Tognarelli
M, Navalesi R. Effects of pantethine on lipids and
apolipoproteins in hypocholesterolemic diabetic and
non-diabetic patients. Current Therapeutic Research.
36:545-549, 1984.
101. Litoff D, Scherzer H, Harrison J. Effects of pantothenic
acid supplementation on human exercise. Med Sci Sports
Exercise. 1985; 17:287(Abstract 17).
102. Moiseenok, A.G., Komar, V.I., Khomich, T.I. et al.
Pantothenic acid in maintaining thiol and immune homeostasis.
Biofactors, 11:53-55, 2000.
103. Department of Health Report on Health and Social Subjects
16: Nutrition and Health in Old Age. London, HMSO, 1979.
104. Fries M.E., Chrisley B.M., Driskell J.A., Vitamin B6
status of a group of preschool children. Am J Clin Nutr 1981;
34: 2806-2810.
105. Schuster K., Bailey L.B., Mahan C.A., Vitamin B6 status
of low-income adolescent and adult pregnant women and the
condition of their infants at birth. Am J Clin Nutr 1981; 34:
1731-1735.
107. Talbott MC, Miller LT, Kerkvliet NI. Pyridoxine
supplementation: Effect on lymphocyte responses in elderly
persons. Am. J. Clin. Nutr. 46:659, 1987.
108. Curhan GC, Willett WC, Speizer FE, Stampfer MJ. Intake of
vitamins B6 and C and the risk of kidney stones in women. J Am
Soc Nephrol. 1999;10(4):840-845.
109. Abraham GE, Hargrove J. Effect of vitamin B6 on
pre-menstrual symptomatology in women with pre-menstrual
syndromes: A double-blind cross-over study. Infertility.
3:155-165, 1980.
110. Webb JL. Nutritional Effects of Oral Contraceptive Use: A
Review. J. Reprod Med, 1980. 25(4):150-6.
111. Prasad AS, Lei KY, Moghissi KS, et al. Effect of Oral
Contraceptives on Nutrients. III. Vitamins B6, B12, and Folic
Acid. Am J Obstet Gynecol, 1976, 125(8):1063-9.
112. Ahmed F, Bamji MS, Iyengar L. Effect of Oral
Contraceptive Agents on Vitamin Nutrition Status. Am J Clin
Nutr. 1975, 28(6):606-15.
114. Haspels AA, Bennink HJ, Schreurs WH. Disturbance of
Tryptophan Metabolism and Its Correction During Oestrogen
Treatment in Postmenopausal Women. Maturitas. 1978,
1(1):15-20.
115. Bermond P. Therapy of Side Effects of Oral Contraceptive
Agents With Vitamin B6. Acta Vitaminal Enzymol. 1982,
4(1-2):45-54.
116. Kishi H, Kishi T, Williams RH, et al. Deficiency of
Vitamin B6 in Women Taking Contraceptive Formulations. Res
Commun Chem Pathol Pharamcol. 1997, 17(2):283-93.
117. Baumblatt MJ, Winston F. Pyridoxine and the pill. Lancet
1970 Apr 18;1(7651):832-833.
118. Rimland B, Callaway E, Dreyfus P. The effect of high
doses of vitamin B6 on autistic children: a double-blind
crossover study. Am J Psychiatry. 1978 Apr;135(4):472-5.
119. Collipp PJ et al, Pyridoxine treatment of childhood
bronchial asthma. Ann Allergy 1975; 35: 93-7.
120. Natta CL et al, Apparent Vitamin B6 deficiency in sickle
cell anaemia. Am J Clin Nutr 1984; 40: 235-9.
121. Vutyavanich T, Wongtra-ngan S, Ruangsri R. Pyridoxine for
nausea and vomiting of pregnancy: a randomized, double-blind,
placebo-controlled trial. Am J Obstet Gynecol. 1995;173(3 Pt
1):881-884.
122. Sahakian V, Rouse D, Sipes S, Rose N, Niebyl J. Vitamin
B6 is effective therapy for nausea and vomiting of pregnancy:
a randomized, double-blind placebo-controlled study. Obstet
Gynecol. 1991;78(1):33-36.
123. Folkers K, Ellis J, Watanabe T, Saji S, Kaji M.
Biochemical evidence for a deficiency of vitamin B6 in the
carpal tunnel syndrome based on a crossover clinical study.
Proc Natl Acad Sci U S A. 1978 Jul;75(7):3410-2.
124. Ellis JM. Treatment of carpal tunnel syndrome with
vitamin B6. Southern Medical Journal. 80:882-884, 1987.
125. Ellis JM et al. Response of vitamin B6 deficiency and the
carpal tunnel syndrome to pyridoxine. Proc Natl Acad Sci USA
79 (1982), 7494-8.
126. Krishnaswamy K, Lakshmi AV. Role of nutritional
supplementation in reducing the levels of homocysteine. J
Assoc Physicians India. 2002 May;50 Suppl:36-42.
127. Leowattana W, Mahanonda N, Bhuripunyo K, Pokum S.
Association between serum homocysteine, vitamin B12, folate
and Thai coronary artery disease patients. J Med Assoc Thai.
2000 May;83(5):536-42.
128. Temple ME, Luzier AB, Kazierad DJ. Homocysteine as a risk
factor for atherosclerosis. Ann Pharmacother. 2000
Jan;34(1):57-65.
129. Lewerin C, Nilsson-Ehle H, Matousek M, Lindstedt G, Steen
B. Reduction of plasma homocysteine and serum methylmalonate
concentrations in apparently healthy elderly subjects after
treatment with folic acid, vitamin B12 and vitamin B6: a
randomised trial. Eur J Clin Nutr. 2003 Nov;57(11):1426-36.
130. J. Selhub, P.F. Jacques, P.W. Wilson, D. Rush, I.H.
Rosenberg. Vitamin status and intake as primary determinants
of homocysteinemia in an elderly population. JAMA, 1993, Dec
8: 2693-2698.
131. Hartman TJ, Woodson K, Stolzenberg-Solomon R, Virtamo J,
Selhub J, Barrett MJ, Albanes D. Association of the B-vitamins
pyridoxal 5'-phosphate (B(6)), B(12), and folate with lung
cancer risk in older men. Am J Epidemiol. 2001 Apr
1;153(7):688-94.
132. Vutyavanich T, Wongtra-ngan S, Ruangsri R. Pyridoxine for
nausea and vomiting of pregnancy: a randomized, double-blind,
placebo-controlled trial. Am J Obstet Gynecol. 1995;173(3 Pt
1):881-884.
133. Doyle W., Crawford M.A., Wynn A.H.A., Wynn S.W., The
Association between Maternal Diet and Birth Dimensions. J Nutr
Med 1990; 1: 9-17.
134. Goutieres F, Aicardi J. Atypical presentations of
pyridoxine dependent seizures: a treatable cause of
intractable epilepsy in infants. Annals of Neurology.
17:117-120, 1985.
135. Reiter LA, Boylan LM, Driskell J, Moak S. Vitamin B-12
and folate intakes and plasma levels of black adolescent
females. J Am Diet Assoc. 1987 Aug;87(8):1065-7.
136. Obeid R, Geisel J, Schorr H, Hubner U, Herrmann W. The
impact of vegetarianism on some haematological parameters. Eur
J Haematol. 2002 Nov-Dec;69(5-6):275-9.
137. Garcia-Arias MT, Villarino Rodriguez A, Garcia-Linares
MC, Rocandio AM, Garcia-Fernandez MC. Iron, folate and
vitamins B12 & C dietary intake of an elderly
institutionalized population in Leon, Spain. Nutr Hosp. 2003
Jul-Aug;18(4):222-5.
138. Baik HW, Russell RM. Vitamin B12 deficiency in the
elderly. Annu Rev Nutr. 1999;19:357-377.
139. Watts DT. Vitamin B12 replacement therapy: how much is
enough? Wis Med J. 1994 May;93(5):203-5.
140. McRae TD, Freedman ML. Why vitamin B12 deficiency should
be managed aggressively. Geriatrics. 1989 Nov;44(11):70-3, 76,
79.
141. Wu K, Helzlsouer KJ, Comstock GW, Hoffman SC, Nadeau MR,
Selhub J. A prospective study on folate, B12, and pyridoxal
5'-phosphate (B6) and breast cancer. Cancer Epidemiol
Biomarkers Prev. 1999;8(3):209-217.
142. Wang HX, Wahlin A, Basun H, Fastbom J, Winblad B,
Fratiglioni L. Vitamin B(12) and folate in relation to the
development of Alzheimer's disease. Neurology.
2001;56(9):1188-1194.
143. Flynn MA, Irvin W, Krause G. The effect of folate and
cobalamin on osteoarthritic hands. J Am Coll Nutr. 1994
Aug;13(4):351-6
144. Saito M, Kato H, Tsuchida T, Konaka C. Chemoprevention
effects on bronchial squamous metaplasia by folate and vitamin
B12 in heavy smokers. Chest. 1994 Aug;106(2):496-9.
145. Heimburger DC, Alexander CB, Birch R, Butterworth CE Jr,
Bailey WC, Krumdieck CL. Improvement in bronchial squamous
metaplasia in smokers treated with folate and vitamin B12.
Report of a preliminary randomized, double-blind intervention
trial. JAMA. 1988 Mar 11;259(10):1525-30.
146. Seror P. Sciatica cured by vitamin B12. Rev Rhum Mal
Osteoartic. 1989 Mar 15;56(4):344.
147. Ostreicher DS. Vitamin B12 supplements as protection
against nitrous oxide inhalation. N Y State Dent J. 1994
Mar;60(3):47-9.
148. Korkina MB, Korchak GM, Medvedev DI. Clinico-experimental
substantiation of the use of carnitine and cobalamin in the
treatment of anorexia nervosa. Zh Nevropatol Psikhiatr Im S S
Korsakova. 1989;89(2):82-7.
149. Kark JD, Sinnreich R, Rosenberg IH, Jacques PF, Selhub J.
Plasma homocysteine and parental myocardial infarction in
young adults in Jerusalem. Circulation. 2002 Jun
11;105(23):2725-9.
150. Zhang G, Dai C. Correlation analysis between plasma
homocysteine level and polymorphism of homocysteine metabolism
related enzymes in ischemic cerebrovascular or cardiovascular
diseases. Zhonghua Xue Ye Xue Za Zhi. 2002 Mar;23(3):126-9.
151. Gao W, Jiang N, Zhu G. The mechanisms of
hyperhomocysteinemia in coronary heart disease. Zhonghua Yi
Xue Za Zhi. 1998 Nov;78(11):821-3.
152. Leowattana W, Mahanonda N, Bhuripunyo K, Pokum S.
Association between serum homocysteine, vitamin B12, folate
and Thai coronary artery disease patients. J Med Assoc Thai.
2000 May;83(5):536-42.
153. Adunsky A, Weitzman A, Fleissig Y, Levenkrohn L, Arad M,
Doolman R, Gavendo S, Sela BA. The relation of plasma total
homocysteine levels to prevalent cardiovascular disease in
older patients with ischemic stroke. Aging (Milano). 2000
Feb;12(1):48-52.
154. Turgan N, Boydak B, Habif S, Apakkan S, Ozmen D, Mutaf I,
Bayindir O. Plasma homocysteine levels in acute coronary
syndromes. Jpn Heart J. 1999 Nov;40(6):729-36.
155. Giles WH, Croft JB, Greenlund KJ, Ford ES, Kittner SJ.
Association between total homocyst(e)ine and the likelihood
for a history of acute myocardial infarction by race and
ethnicity: Results from the Third National Health and
Nutrition Examination Survey. Am Heart J. 2000
Mar;139(3):446-53.
156. Temple ME, Luzier AB, Kazierad DJ. Homocysteine as a risk
factor for atherosclerosis. Ann Pharmacother. 2000
Jan;34(1):57-65.
158. Whincup PH, Refsum H, Perry IJ, Morris R, Walker M,
Lennon L, Thomson A, Ueland PM, Ebrahim SB. Serum total
homocysteine and coronary heart disease: prospective study in
middle aged men. Heart. 1999 Oct;82(4):448-54.
159. Bots ML, Launer LJ, Lindemans J, Hoes AW, Hofman A,
Witteman JC, Koudstaal PJ, Grobbee DE. Homocysteine and
short-term risk of myocardial infarction and stroke in the
elderly: the Rotterdam Study. Arch Intern Med. 1999 Jan
11;159(1):38-44.
160. Stehouwer CD, Weijenberg MP, van den Berg M, Jakobs C,
Feskens EJ, Kromhout D. Serum homocysteine and risk of
coronary heart disease and cerebrovascular disease in elderly
men: a 10-year follow-up. Arterioscler Thromb Vasc Biol. 1998
Dec;18(12):1895-901.
161. Verhoef P, Kok FJ, Kruyssen DA, Schouten EG, Witteman JC,
Grobbee DE, Ueland PM, Refsum H. Plasma total homocysteine, B
vitamins, and risk of coronary atherosclerosis. Arterioscler
Thromb Vasc Biol. 1997 May;17(5):989-95.
162. Krishnaswamy K, Lakshmi AV. Role of nutritional
supplementation in reducing the levels of homocysteine. J
Assoc Physicians India. 2002 May;50 Suppl:36-42.
163. J. Selhub, P.F. Jacques, P.W. Wilson, D. Rush, I.H.
Rosenberg. Vitamin status and intake as primary determinants
of homocysteinemia in an elderly population. JAMA, 1993, Dec
8: 2693-2698.
164. Stanger O, Herrmann W, Pietrzik K, Fowler B, Geisel J,
Dierkes J, Weger M. DACH-LIGA homocystein (german, austrian
and swiss homocysteine society): consensus paper on the
rational clinical use of homocysteine, folic acid and
B-vitamins in cardiovascular and thrombotic diseases:
guidelines and recommendations. Clin Chem Lab Med. 2003
Nov;41(11):1392-403.
165. Krishnaswamy K, Lakshmi AV. Role of nutritional
supplementation in reducing the levels of homocysteine. J
Assoc Physicians India. 2002 May;50 Suppl:36-42.
166. Leowattana W, Mahanonda N, Bhuripunyo K, Pokum S.
Association between serum homocysteine, vitamin B12, folate
and Thai coronary artery disease patients. J Med Assoc Thai.
2000 May;83(5):536-42.
167. Temple ME, Luzier AB, Kazierad DJ. Homocysteine as a risk
factor for atherosclerosis. Ann Pharmacother. 2000
Jan;34(1):57-65.
168. Lewerin C, Nilsson-Ehle H, Matousek M, Lindstedt G, Steen
B. Reduction of plasma homocysteine and serum methylmalonate
concentrations in apparently healthy elderly subjects after
treatment with folic acid, vitamin B12 and vitamin B6: a
randomised trial. Eur J Clin Nutr. 2003 Nov;57(11):1426-36.
169. Seshadri S, Beiser A, Selhub J, et al. Plasma
homocysteine as a risk factor for dementia and Alzheimer's
disease. N Engl J Med. 2002;346(7):476-483.
170. Hutto BR. Folate and cobalamin in psychiatric illness.
Compr Psychiatry. 1997;38(6):305-314.
171. Penninx BW, Guralnik JM, Ferrucci L, Fried LP, Allen RH,
Stabler SP. Vitamin B(12) deficiency and depression in
physically disabled older women: epidemiologic evidence from
the Women's Health and Aging Study. Am J Psychiatry.
2000;157(5):715-721.
172. Edwin E, Holten K, Norum KR, Schrumpf A, Skaug OE.
Vitamin B12 Hypovitaminosis in Mental Diseases. Acta Medical
Scandinavica. 1965;177:689-699.
173. Bryan J, Calvaresi E, Hughes D. Short-term folate,
vitamin B-12 or vitamin B-6 supplementation slightly affects
memory performance but not mood in women of various ages. J
Nutr. 2002 Jun;132(6):1345-56.
174. Newbold HL. Vitamin B-12: placebo or neglected
therapeutic tool? Med Hypotheses. 1989 Mar;28(3):155-64.
175. La Rue A, Koehler KM, Wayne SJ, Chiulli SJ, Haaland KY,
Garry PJ. Nutritional status and cognitive functioning in a
normally aging sample: a 6-y reassessment. Am J Clin Nutr.
1997 Jan;65(1):20-9.
176. Rajan S, Wallace JI, Beresford SA, Brodkin KI, Allen RA,
Stabler SP. Screening for cobalamin deficiency in geriatric
outpatients: prevalence and influence of synthetic cobalamin
intake. J Am Geriatr Soc. 2002 Apr;50(4):624-30.
177. Bopp-Kistler I, Ruegger-Frey B, Grob D, Six P. Vitamin
B12 deficiency in geriatrics. Schweiz Rundsch Med Prax. 1999
Nov 4;88(45):1867-75.
178. Gonzalez-Gross M, Prinz-Langenohl R, Pietrzik K. Folate
status in Germany 1997-2000. Int J Vitam Nutr Res. 2002
Dec;72(6):351-9.
179. Hilton JJ. Folic acid intake of young women. J Obstet
Gynecol Neonatal Nurs. 2002 Mar-Apr;31(2):172-7.
180. Konings EJ, Roomans HH, Dorant E, Goldbohm RA, Saris WH,
van den Brandt PA. Folate intake of the Dutch population
according to newly established liquid chromatography data for
foods. Am J Clin Nutr. 2001 Apr;73(4):765-76.
181. Clarke R, Grimley Evans J, Schneede J, Nexo E, Bates C,
Fletcher A, Prentice A, Johnston C, Ueland PM, Refsum H,
Sherliker P, Birks J, Whitlock G, Breeze E, Scott JM. Vitamin
B12 and folate deficiency in later life. Age Ageing. 2004
Jan;33(1):34-41.
182. Figlin E, Chetrit A, Shahar A, Shpilberg O, Zivelin A,
Rosenberg N, Brok-Simoni F, Gadoth N, Sela BA, Seligsohn U.
High prevalences of vitamin B12 and folic acid deficiency in
elderly subjects in Israel. Br J Haematol. 2003
Nov;123(4):696-701.
183. Hultberg B, Nilsson K, Isaksson A, Gustafson L. Folate
deficiency is a common finding in psychogeriatric patients.
Aging Clin Exp Res. 2002 Dec;14(6):479-84.
184. Serra-Majem L, Ribas L, Ngo J, Aranceta J, Garaulet M,
Carazo E, Mataix J, Perez-Rodrigo C, Quemada M, Tojo R,
Vazquez C. Risk of inadequate intakes of vitamins A, B1, B6,
C, E, folate, iron and calcium in the Spanish population aged
4 to 18.
185. Int J Vitam Nutr Res. 2001 Nov;71(6):325-31. Wright JD,
Bialostosky K, Gunter EW, Carroll MD, Najjar MF, Bowman BA,
Johnson CL. Blood folate and vitamin B12: United States,
1988-94. Vital Health Stat 11. 1998 Dec;(243):1-78.
186. Villarino Rodriguez A, Garcia-Linares Mdel C,
Garcia-Arias MT, Garcia-Fernandez Mdel C. Anthropometric
assessment and vitamin intake by a group of elderly
institucionalized individuals in the province of Leon (Spain).
Nutr Hosp. 2002 Nov-Dec;17(6):290-5.
187. Morris MS, Fava M, Jacques PF, Selhub J, Rosenberg IH.
Depression and folate status in the US Population. Psychother
Psychosom. 2003 Mar-Apr;72(2):80-7.
188. Fuchs I, Omansky L, Lerner Y. Folic acid deficiency in
chronically hospitalized mental patients. Harefuah. 1998
Sep;135(5-6):186-7, 255.
189. Kelly GS. Folates: supplemental forms and therapeutic
applications. Altern Med Rev. 1998 Jun;3(3):208-20.
190. Giovannucci E, Stampfer MJ, Colditz GA, Hunter DJ, Fuchs
C, Rosner BA, Speizer FE, Willett WC. Multivitamin use,
folate, and colon cancer in women in the Nurses' Health Study.
Ann Intern Med. 1998 Oct 1;129(7):517-24.
191. Mayne ST, Risch HA, Dubrow R, Chow WH, Gammon MD, Vaughan
TL, Farrow DC, Schoenberg JB, Stanford JL, Ahsan H, West AB,
Rotterdam H, Blot WJ, Fraumeni JF Jr. Nutrient intake and risk
of subtypes of esophageal and gastric cancer. Cancer Epidemiol
Biomarkers Prev. 2001 Oct;10(10):1055-62.
192. Zhu S, Mason J, Shi Y, Hu Y, Li R, Wahg M, Zhou Y, Jin G,
Xie Y, Wu G, Xia D, Qian Z, Sohg H, Zhang L, Russell R, Xiao
S. The effect of folic acid on the development of stomach and
other gastrointestinal cancers. Chin Med J (Engl). 2003
Jan;116(1):15-9.
193. Jacques PF, Chylack LT Jr, Hankinson SE, Khu PM, Rogers
G, Friend J, Tung W, Wolfe JK, Padhye N, Willett WC, Taylor A.
Long-term nutrient intake and early age-related nuclear lens
opacities. Arch Ophthalmol. 2001 Jul;119(7):1009-19.
194. Mangoni AA, Sherwood RA, Swift CG, Jackson SH. Folic acid
enhances endothelial function and reduces blood pressure in
smokers: a randomized controlled trial. J Intern Med. 2002
Dec;252(6):497-503.
195. Kendler BS. Nutritional strategies in cardiovascular
disease control: an update on vitamins and conditionally
essential nutrients. Prog Cardiovasc Nurs. 1999
Autumn;14(4):124-9.
196. Tonstad S, Refsum H, Ueland PM. Association between
plasma total homocysteine and parental history of
cardiovascular disease in children with familial
hypercholesterolemia. Circulation. 1997 Sep 16;96(6):1803-8.
197. Schwartz SM, Siscovick DS, Malinow MR, Rosendaal FR,
Beverly RK, Hess DL, Psaty BM, Longstreth WT Jr, Koepsell TD,
Raghunathan TE, Reitsma PH. Myocardial infarction in young
women in relation to plasma total homocysteine, folate, and a
common variant in the methylenetetrahydrofolate reductase
gene. Circulation. 1997 Jul 15;96(2):412-7.
198. Neal B, MacMahon S, Ohkubo T, Tonkin A, Wilcken D;
PACIFIC Study Group. Dose-dependent effects of folic acid on
plasma homocysteine in a randomized trial conducted among 723
individuals with coronary heart disease. Eur Heart J. 2002
Oct;23(19):1509-15.
199. Hernandez-Diaz S, Martinez-Losa E, Fernandez-Jarne E,
Serrano-Martinez M, Martinez-Gonzalez MA. Dietary folate and
the risk of nonfatal myocardial infarction. Epidemiology. 2002
Nov;13(6):700-6.
200. Marcucci R, Zanazzi M, Bertoni E, Rosati A, Fedi S, Lenti
M, Prisco D, Castellani S, Abbate R, Salvadori M. Vitamin
supplementation reduces the progression of atherosclerosis in
hyperhomocysteinemic renal-transplant recipients.
Transplantation. 2003 May 15;75(9):1551-5.
201. McNulty H, Cuskelly GJ, Ward M. Response of red blood
cell folate to intervention: implications for folate
recommendations for the prevention of neural tube defects. Am
J Clin Nutr. 2000;71(5 Suppl):1308S-1311S.
202. Kondo A, Kimura K, Isobe Y, Kamihira O, Matsuura O, Gotoh
M, Okai I. Folic acid reduces risks of having fetus affected
with neural tube defects: dietary food folate and plasma
folate concentration. Nippon Hinyokika Gakkai Zasshi. 2003
Jul;94(5):551-9.
203. Bailey LB, Rampersaud GC, Kauwell GP. Folic acid
supplements and fortification affect the risk for neural tube
defects, vascular disease and cancer: evolving science. J
Nutr. 2003 Jun;133(6):1961S-1968S.
204. Rosenberg KD, Gelow JM, Sandoval AP. Pregnancy
intendedness and the use of periconceptional folic acid.
Pediatrics. 2003 May;111(5 Part 2):1142-5.
205. Hernandez-Diaz S, Werler MM, Louik C, Mitchell AA. Risk
of gestational hypertension in relation to folic acid
supplementation during pregnancy. Am J Epidemiol. 2002 Nov
1;156(9):806-12.
206. Kauwell GP, Lippert BL, Wilsky CE, Herrlinger-Garcia K,
Hutson AD, Theriaque DW, Rampersaud GC, Cerda JJ, Bailey LB.
Folate status of elderly women following moderate folate
depletion responds only to a higher folate intake. J Nutr.
2000 Jun;130(6):1584-90.
207. Elkin AC, Higham J. Folic acid supplements are more
effective than increased dietary folate intake in elevating
serum folate levels. BJOG. 2000 Feb;107(2):285-9.
208. Kiely M, Flynn A, Harrington KE, Robson PJ, O'Connor N,
Hannon EM, O'Brien MM, Bell S, Strain JJ. The efficacy and
safety of nutritional supplement use in a representative
sample of adults in the North/South Ireland Food Consumption
Survey. Public Health Nutr. 2001 Oct;4(5A):1089-97.
209. Oakley GP Jr, Adams MJ, Dickinson CM. More folic acid for
everyone, now. J Nutr. 1996 Mar;126(3):751S-755S.
210. Brouwer DA, Welten HT, van Doormaal JJ, Reijngoud DJ,
Muskiet FA. Recommended dietary allowance of folic acid is
insufficient for optimal homocysteine levels. Ned Tijdschr
Geneeskd. 1998 Apr 4;142(14):782-6.
211. Ames BN. Micronutrients prevent cancer and delay aging.
Toxicol Lett. 1998 Dec 28;102-103:5-18.
212. Laszlo A, Schuler EA, Sallay E, Endreffy E, Somogyi C,
Varkonyi A, Havass Z, Jansen KP, Wolf B. Neonatal screening
for biotinidase deficiency in Hungary: clinical, biochemical
and molecular studies. J Inherit Metab Dis. 2003;26(7):693-8.
213. Joshi S, al-Essa MA, Archibald A, Ozand PT. Biotinidase
deficiency: a treatable genetic disorder in the Saudi
population. East Mediterr Health J. 1999 Nov;5(6):1213-7.
214. Molteno C, Smit I, Mills J, Huskisson J. Nutritional
status of patients in a long-stay hospital for people with
mental handicap. S Afr Med J. 2000 Nov;90(11):1135-40.
215. Pomponio RJ, Coskun T, Demirkol M, Tokatli A, Ozalp I,
Huner G, Baykal T, Wolf B. Novel mutations cause biotinidase
deficiency in Turkish children. J Inherit Metab Dis. 2000
Mar;23(2):120-8.
216. Bonjour JP. Biotin in man's nutrition and therapy -- a
review. Int J Vitam Nutr Res. 1977;47(2):107-18.
217. Taitz LS, Leonard JV, Bartlett K. Longterm auditory and
visual complications of biotinidase deficiency. Early Hum Dev
1985 Sep;11(34):32531.
218. Wastell HJ, Bartlett K, Dale G, Shein A. Biotinidase
deficiency: a survey of 10 cases. Arch Dis Child 1988
Oct;63(10):12449.
219. Ames BN. A role for supplements in optimizing health: the
metabolic tune-up. Arch Biochem Biophys. 2004 Mar
1;423(1):227-34.
220. Furukawa Y. Enhancement of glucoseinduced insulin
secretion and modification of glucose metabolism by biotin.
Nippon rinsho (JAPAN) Oct 1999, 57 (10) p22619.
221. Koutsikos D.; Fourtounas C.; Kapetanaki A.; Agroyannis
B.; Tzanatos H.;
Rammos G.; Kopelias I.; Bosiolis B.; Bovoleti O.; Darema M.;
Sallum G. Oral glucose tolerance test after highdose i.v.
biotin administration in normoglucemic hemodialysis patients.
Renal Failure. 1996, 18/1 (131137).
222. Med Hypotheses 2000 Mar;54(3):4837.
223. Maebashi Masaru; Makino Yoshio; Furukawa Yuji(a); Ohinata
Kosaku; Kimura Shuichi. Therapeutic evaluation of the effect
of biotin on hyperglycemia in patients with noninsulin
dependent diabetes mellitus. Journal of Clinical Biochemistry
and Nutrition 1993 14 ( 3 ): p 211-218.
224. Med Hypotheses 2000 Mar;54(3):4837.
225. McCarty MF. Highdose biotin, an inducer of glucokinase
expression, may synergize with chromium picolinate to enable a
definitive nutritional therapy for type II diabetes. Medical
hypotheses. May 1999, 52 (5) p4016.
226. McCarty M.F. Towards practical prevention of type 2
diabetes. Medical Hypotheses. 2000, 54/5 (786793).
227. Koutsikos D, Agroyannis B, Tzanatos Exarchou H. Biotin
for diabetic peripheral neuropathy. Biomed Pharmacother
1990;44(10):5114.
228. Shelley WB, Shelley ED. Uncombable hair syndrome:
observations on response to biotin and occurrence in siblings
with ectodermal dysplasia. J Am Acad Dermatol. 1985
Jul;13(1):97-102.
229. Diet, Nutrition and the Prevention of Chronic Diseases.
WHO Technical Report Series. Report of a Joint WHO/FAO Expert
Consultation. Geneva 2003. p. 72.
230. Chapman KM, Ham JO, Pearlman RA. Longitudinal assessment
of the nutritional status of elderly veterans. J Gerontol A
Biol Sci Med Sci. 1996 Jul;51(4):B261-9.
231. Yin S, Su Y, Liu Q, Zhang M. Dietary status of preschool
children from day-care kindergartens in six cites of China.
Wei Sheng Yan Jiu. 2002 Oct;31(5):375-8.
232. Weinstein M, Babyn P, Zlotkin S. An orange a day keeps
the doctor away: scurvy in the year 2000. Pediatrics. 2001
Sep;108(3):E55.
233. Hampl JS, Taylor CA, Johnston CS. Intakes of vitamin C,
vegetables and fruits: which schoolchildren are at risk? J Am
Coll Nutr. 1999 Dec;18(6):582-90.
234. Vannucchi H, da Cunha DF, Bernardes MM, Unamuno MR.
Brasil. Serum levels of vitamin A, E, C and B2, carotenoid and
zinc in hospitalized elderly patients. Rev Saude Publica. 1994
Apr;28(2):121-6.
235. Boulinguez S, Bouyssou-Gauthier M, De Vencay P, Bedane C,
Bonnetblanc J. Scurvy presenting with ecchymotic purpura and
hemorrhagic ulcers of the lower limbs. Ann Dermatol Venereol.
2000 May;127(5):510-2.
236. Werbach MR. Nutritional strategies for treating chronic
fatigue syndrome. Altern Med Rev. 2000 Apr;5(2):93-108.
237. Dejmek J, Ginter E, Solansky I, Podrazilova K, Stavkova
Z, Benes I, Sram RJ. Vitamin C, E and A levels in maternal and
fetal blood for Czech and Gypsy ethnic groups in the Czech
Republic. Int J Vitam Nutr Res. 2002 May;72(3):183-90.
238. Clow CL, Laberge C, Scriver CR. Neonatal hypertyrosinemia
and evidence for deficiency of ascorbic acid in Arctic and
subarctic peoples. Can Med Assoc J. 1975 Oct 4;113(7):624-6.
239. Sauberlich HE. Human requirements and needs. Vitamin C
status: methods and findings. Ann N Y Acad Sci. 1975 Sep
30;258:438-50.
240. Dawson KP, Richardson WW, Orsborn CE. The leucocyte
ascorbic acid levels of children in hospital. N Z Med J. 1977
Feb 23;85(582):141-3. 4.
241. Stephen R, Utecht T. Scurvy identified in the emergency
department: a case report. J Emerg Med. 2001;21(3):235-237.
242. Tabet N, Mantle D, Walker Z, Orrell M. Endogenous
antioxidant activities in relation to concurrent vitamins A,
C, and E intake in dementia. Int Psychogeriatr. 2002
Mar;14(1):7-15.
243. Sudha K, Rao AV, Rao A. Oxidative stress and antioxidants
in epilepsy. Clin Chim Acta. 2001 Jan;303(1-2):19-24.
244. Kharb S. Vitamin E and C in preeclampsia. Eur J Obstet
Gynecol Reprod Biol. 2000 Nov;93(1):37-9.
245. Panburana P, Phuapradit W, Puchaiwatananon O. Antioxidant
nutrients and lipid peroxide levels in Thai preeclamptic
pregnant women. J Obstet Gynaecol Res. 2000 Oct;26(5):377-81.
246. Simon JA, Hudes ES. Serum ascorbic acid and gallbladder
disease prevalence among US adults: the Third National Health
and Nutrition Examination Survey (NHANES III). Arch Intern
Med. 2000 Apr 10;160(7):931-6.
247. Suboticanec K, Folnegovic-Smalc V, Turcin R, Mestrovic B,
Buzina R. Plasma levels and urinary vitamin C excretion in
schizophrenic patients.
248. Hum Nutr Clin Nutr. 1986 Nov;40(6):421-8. Suboticanec K,
Folnegovic-Smalc V, Korbar M, Mestrovic B, Buzina R. Vitamin C
status in chronic schizophrenia. Biol Psychiatry. 1990 Dec
1;28(11):959-66.
249. Delport R, Ubbink JB, Human JA, Becker PJ, Myburgh DP,
Vermaak WJ. Antioxidant vitamins and coronary artery disease
risk in South African males. Clin Chim Acta. 1998
Nov;278(1):55-60.
250. Singh RB, Ghosh S, Niaz MA, Singh R, Beegum R, Chibo H,
Shoumin Z, Postiglione A. Dietary intake, plasma levels of
antioxidant vitamins, and oxidative stress in relation to
coronary artery disease in elderly subjects. Am J Cardiol.
1995 Dec 15;76(17):1233-8.
251. Singh RB, Niaz MA, Bishnoi I, Sharma JP, Gupta S, Rastogi
SS, Singh R, Begum R, Chibo H, Shoumin Z. Diet, antioxidant
vitamins, oxidative stress and risk of coronary artery
disease: the Peerzada Prospective Study. Acta Cardiol.
1994;49(5):453-67.
252. Gey KF. Vitamins E plus C and interacting conutrients
required for optimal health. A critical and constructive
review of epidemiology and supplementation data regarding
cardiovascular disease and cancer. Biofactors.
1998;7(1-2):113-74.
253. Akkus I, Saglam NI, Caglayan O, Vural H, Kalak S, Saglam
M. Investigation of erythrocyte membrane lipid peroxidation
and antioxidant defense systems of patients with coronary
artery disease (CAD) documented by angiography. Clin Chim
Acta. 1996 Jan 31;244(2):173-80.
254. Chen JH, Liu XJ, Wang QC, Zeng H, Jiang XP. Study on the
changes in endogenous oxidation agents and levels of
anti-oxidation agents in patients with cerebral vascular
disease. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2003
Apr;15(4):232-4.
255. Skrzydlewska E, Kozuszko B, Sulkowska M, Bogdan Z,
Kozlowski M, Snarska J, Puchalski Z, Sulkowski S, Skrzydlewski
Z. Antioxidant potential in esophageal, stomach and colorectal
cancers. Hepatogastroenterology. 2003 Jan-Feb;50(49):126-31.
256. Beno I, Ondreicka R, Magalova T, Brtkova A, Grancicova E.
Precancerous conditions and carcinomas of the stomach and
colorectum--blood levels of selected micronutrients. Bratisl
Lek Listy. 1997 Dec;98(12):674-7.
257. Choi MA, Kim BS, Yu R. Serum antioxidative vitamin levels
and lipid peroxidation in gastric carcinoma patients. Cancer
Lett. 1999 Feb 8;136(1):89-93.
258. Yokoyama T, Date C, Kokubo Y, Yoshiike N, Matsumura Y,
Tanaka H. Serum vitamin C concentration was inversely
associated with subsequent 20-year incidence of stroke in a
Japanese rural community. The Shibata study. Stroke. 2000
Oct;31(10):2287-94.
259. You WC, Zhang L, Gail MH, Chang YS, Liu WD, Ma JL, Li JY,
Jin ML, Hu YR, Yang CS, Blaser MJ, Correa P, Blot WJ, Fraumeni
JF Jr, Xu GW. Gastric dysplasia and gastric cancer:
Helicobacter pylori, serum vitamin C, and other risk factors.
J Natl Cancer Inst. 2000 Oct 4;92(19):1607-12.
260. Kodama M, Kodama T. In search of the cause of gastric
cancer. In Vivo. 2000 Jan-Feb;14(1):125-38.
261. Dabrowska-Ufniarz E, Dzieniszewski J, Jarosz M,
Wartanowicz M. Vitamin C concentration in gastric juice in
patients with precancerous lesions of the stomach and gastric
cancer. Med Sci Monit. 2002 Feb;8(2):CR96-103.
262. Nishida M, Grossi SG, Dunford RG, Ho AW, Trevisan M,
Genco RJ. Dietary vitamin C and the risk for periodontal
disease. J Periodontol. 2000 Aug;71(8):1215-23.
263. Rath M, Pauling L. Solution to the puzzle of human
cardiovascular disease: Its primary cause is ascorbate
deficiency, leading to the deposition of lipoprotein (a) and
fibrinogen/fibrin in the vascular wall. Journal of
Orthomolecular Medicine. 1991; 6:125-134.
264. De Stefani E, Boffetta P, Brennan P, Deneo-Pellegrini H,
Carzoglio JC, Ronco A, Mendilaharsu M. Dietary carotenoids and
risk of gastric cancer: a case-control study in Uruguay. Eur J
Cancer Prev. 2000 Oct;9(5):329-34.
265. La Vecchia C, D'Avanzo B, Negri E, Decarli A, Benichou J.
Attributable risks for stomach cancer in northern Italy. Int J
Cancer. 1995 Mar 16;60(6):748-52.
266. Ekstrom AM, Serafini M, Nyren O, Hansson LE, Ye W, Wolk
A. Dietary antioxidant intake and the risk of cardia cancer
and noncardia cancer of the intestinal and diffuse types: a
population-based case-control study in Sweden. Int J Cancer.
2000 Jul 1;87(1):133-40.
267. Feiz HR, Mobarhan S. Does vitamin C intake slow the
progression of gastric cancer in Helicobacter pylori-infected
populations? Nutr Rev. 2002 Jan;60(1):34-6.
268. Valle J, Gisbert JP. Helicobacter pylori infection and
precancerous lesions of the stomach. Hepatogastroenterology.
2001 Nov-Dec;48(42):1548-51.
269. Zhang L, Blot WJ, You WC, Chang YS, Liu XQ, Kneller RW,
Zhao L, Liu WD, Li JY, Jin ML, et al. Serum micronutrients in
relation to pre-cancerous gastric lesions. Int J Cancer. 1994
Mar 1;56(5):650-4.
270. Terry P, Lagergren J, Ye W, Nyren O, Wolk A. Antioxidants
and cancers of the esophagus and gastric cardia. Int J Cancer.
2000 Sep 1;87(5):750-4.
271. Mirvish SS. Experimental evidence for inhibition of
N-nitroso compound formation as a factor in the negative
correlation between vitamin C consumption and the incidence of
certain cancers. Cancer Res. 1994 Apr 1;54(7
Suppl):1948s-1951s.
272. Jacques PF, Chylack LT Jr, Hankinson SE, Khu PM, Rogers
G, Friend J, Tung W, Wolfe JK, Padhye N, Willett WC, Taylor A.
Long-term nutrient intake and early age-related nuclear lens
opacities. Arch Ophthalmol. 2001 Jul;119(7):1009-19.
273. . Jacques PF. The potential preventive effects of
vitamins for cataract and age-related macular degeneration.
Int J Vitam Nutr Res. 1999 May;69(3):198-205.
274. Brubaker RF, Bourne WM, Bachman LA, McLaren JW. Ascorbic
acid content of human corneal epithelium. Invest Ophthalmol
Vis Sci. 2000 Jun;41(7):1681-3.
275. Schindler TH, Lewandowski E, Olschewski M, Hasler K,
Solzbach U, Just H. Effect of vitamin c on platelet
aggregation in smokers and nonsmokers. Med Klin. 2002 May
15;97(5):263-9.
276. Osganian SK, Stampfer MJ, Rimm E, Spiegelman D, Hu FB,
Manson JE, Willett WC. Vitamin C and risk of coronary heart
disease in women. J Am Coll Cardiol. 2003 Jul 16;42(2):246-52.
277. Fang JC, Kinlay S, Beltrame J, Hikiti H, Wainstein M,
Behrendt D, Suh J, Frei B, Mudge GH, Selwyn AP, Ganz P. Effect
of vitamins C and E on progression of transplant-associated
arteriosclerosis: a randomised trial. Lancet. 2002 Mar
30;359(9312):1108-13.
278. Rath M, Pauling L. A unified theory of human
cardiovascular disease leading the way to the abolition of
this disease as a cause for human mortality. Journal of
Orthomolecular Medicine. 1992; 7:5-15.
279. Rath M. Reducing the risk for cardiovascular disease with
nutritional supplements. Journal of Orthomolecular Medicine.
1992; 7:153-162.
280. Rath M, Niedzwiecki A. Nutritional Supplement Program
Halts Progression of Early Coronary Atherosclerosis Documented
by Ultrafast Computed Tomography. Journal of Applied
Nutrition. 1996; 48:68-78.
281. Salonen JT, Nyyssonen K, Salonen R, Lakka HM, Kaikkonen
J, Porkkala-Sarataho E, Voutilainen S, Lakka TA, Rissanen T,
Leskinen L, Tuomainen TP, Valkonen VP, Ristonmaa U, Poulsen
HE. Antioxidant Supplementation in Atherosclerosis Prevention
(ASAP) study: a randomized trial of the effect of vitamins E
and C on 3-year progression of carotid atherosclerosis. J
Intern Med. 2000 Nov;248(5):377-86.
282. Brown DJ, Goodman J. A review of vitamins A, C, and E and
their relationship to cardiovascular disease. Clin Excell
Nurse Pract. 1998 Jan;2(1):10-22.
283. Rath M, Niedzwiecki A. Progression of early stages of
coronary calcifications can be stopped by the synergistic
effect of vitamins and essential nutrients. Atherosclerosis.
1997; 134:333.
284. Kendler BS. Nutritional strategies in cardiovascular
disease control: an update on vitamins and conditionally
essential nutrients. Prog Cardiovasc Nurs. 1999
Autumn;14(4):124-9.
285. Gey KF, Stahelin HB, Ballmer PE. Essential antioxidants
in cardiovascular diseases--lessons for Europe. Ther Umsch.
1994 Jul;51(7):475-82.
286. Eichholzer M, Stahelin HB, Gey KF. Inverse correlation
between essential antioxidants in plasma and subsequent risk
to develop cancer, ischemic heart disease and stroke
respectively: 12-year follow-up of the Prospective Basel
Study. EXS. 1992;62:398-410.
287. Enstrom JE, Kanim LE, Klein MA. Vitamin C intake and
mortality among a sample of the United States population.
Epidemiology. 1992 May;3(3):194-202.
288. Simon JA, Hudes ES, Tice JA. Relation of serum ascorbic
acid to mortality among US adults. J Am Coll Nutr. 2001
Jun;20(3):255-63.
289. Sinatra ST, DeMarco J. Free radicals, oxidative stress,
oxidized low density lipoprotein (LDL), and the heart:
antioxidants and other strategies to limit cardiovascular
damage. Conn Med. 1995 Oct;59(10):579-88.
290. Flagg EW, Coates RJ, Greenberg RS. Epidemiologic studies
of antioxidants and cancer in humans. J Am Coll Nutr. 1995
Oct;14(5):419-27.
291. Block G. Epidemiologic evidence regarding vitamin C and
cancer. Am J Clin Nutr. 1991 Dec;54(6 Suppl):1310S-1314S.
292. Kikuchi S. Epidemiology of Helicobacter pylori and
gastric cancer. Gastric Cancer. 2002;5(1):6-15.
293. Mayne ST, Risch HA, Dubrow R, Chow WH, Gammon MD, Vaughan
TL, Farrow DC, Schoenberg JB, Stanford JL, Ahsan H, West AB,
Rotterdam H, Blot WJ, Fraumeni JF Jr. Nutrient intake and risk
of subtypes of esophageal and gastric cancer. Cancer Epidemiol
Biomarkers Prev. 2001 Oct;10(10):1055-62.
294. Hansson LE, Nyren O, Bergstrom R, Wolk A, Lindgren A,
Baron J, Adami HO. Nutrients and gastric cancer risk. A
population-based case-control study in Sweden. Int J Cancer.
1994 Jun 1;57(5):638-44.
295. Cohen M. Ascorbic acid and gastrointestinal cancer. J Am
Coll Nutr. 1995 Dec;14(6):565-78.
296. Zhang L, Zhao L, Ma J. Relationship between serum
micronutrients and precancerous gastric lesions. Zhonghua Yu
Fang Yi Xue Za Zhi. 1995 Jul;29(4):198-201.
298. Do MH, Lee SS, Jung PJ, Lee MH. Intake of dietary fat and
vitamin in relation to breast cancer risk in korean women: a
case-control study. J Korean Med Sci. 2003 Aug;18(4):534-40.
299. Zhang S, Hunter DJ, Forman MR, Rosner BA, Speizer FE,
Colditz GA, Manson JE, Hankinson SE, Willett WC. Dietary
carotenoids and vitamins A, C, and E and risk of breast
cancer. J Natl Cancer Inst. 1999 Mar 17;91(6):547-56.
300. Van Hoydonck PG, Temme EH, Schouten EG. A dietary
oxidative balance score of vitamin c, beta-carotene and iron
intakes and mortality risk in male smoking Belgians. J Nutr.
2002 Apr;132(4):756-61.
301. Grzegorczyk K, Rutkowski M, Drozda R. Vitamin C in
treatment of certain cardiovascular diseases. Pol Merkuriusz
Lek. 2001 Feb;10(56):122-5.
302. Paolisso G, Balbi V, Volpe C, Varricchio G, Gambardella
A, Saccomanno F, Ammendola S, Varricchio M, D'Onofrio F.
Metabolic benefits deriving from chronic vitamin c
supplementation in aged non-insulin dependent diabetics. J Am
Coll Nutr. 1995 Aug;14(4):387-92.
303. Sargeant LA, Wareham NJ, Bingham S, Day NE, Luben RN,
Oakes S, Welch A, Khaw KT. Vitamin C and hyperglycemia in the
European Prospective Investigation into Cancer--Norfolk
(EPIC-Norfolk) study: a population-based study. Diabetes Care.
2000 Jun;23(6):726-32.
304. Nathens AB, Neff MJ, Jurkovich GJ, Klotz P, Farver K,
Ruzinski JT, Radella F, Garcia I, Maier RV. Randomized,
prospective trial of antioxidant supplementation in critically
ill surgical patients. Ann Surg. 2002 Dec;236(6):814-22.
305. Hajjar IM, George V, Sasse EA, Kochar MS. A randomized,
double-blind, controlled trial of vitamin C in the management
of hypertension and lipids. Am J Ther. 2002
Jul-Aug;9(4):289-93.
306. Brody S, Preut R, Schommer K, Schurmeyer TH. A randomized
controlled trial of high dose ascorbic acid for reduction of
blood pressure, cortisol, and subjective responses to
psychological stress. Psychopharmacology (Berl). 2002
Jan;159(3):319-24. Epub 2001 Nov 20.
307. Sherman DL, Keaney JF Jr, Biegelsen ES, Duffy SJ, Coffman
JD, Vita JA. Pharmacological concentrations of ascorbic acid
are required for the beneficial effect on endothelial
vasomotor function in hypertension. Hypertension. 2000
Apr;35(4):936-41.
308. Fotherby MD, Williams JC, Forster LA, Craner P, Ferns GA.
Effect of vitamin C on ambulatory blood pressure and plasma
lipids in older persons. J Hypertens. 2000 Apr;18(4):411-5.
309. Mullan BA, Young IS, Fee H, McCance DR. Ascorbic acid
reduces blood pressure and arterial stiffness in type 2
diabetes. Hypertension. 2002 Dec;40(6):804-9.
310. Vitamins C and E levels greater than the RDA are
associated with prevention of ovarian cancer. Fleischauer AT,
Olson SH, Mignone L, Simonsen N, Caputo TA, Harlap S. Dietary
antioxidants, supplements, and risk of epithelial ovarian
cancer. Nutr Cancer. 2001;40(2):92-8.
311. Schaafsma A, de Vries PJ, Saris WH. Delay of natural bone
loss by higher intakes of specific minerals and vitamins. Crit
Rev Food Sci Nutr. 2001 May;41(4):225-49.
312. Morton DJ, Barrett-Connor EL, Schneider DL. Vitamin C
supplement use and bone mineral density in postmenopausal
women. J Bone Miner Res. 2001 Jan;16(1):135-40.
313. Melhus H, Michaelsson K, Holmberg L, Wolk A, Ljunghall S.
106Smoking, antioxidant vitamins, and the risk of hip
fracture. J Bone Miner Res. 1999 Jan;14(1):129-35).
314. Hemila H. Vitamin c and the common cold. Br J Nutr. 1992
Jan;67(1):3-16. Van Straten M, Josling P. Preventing the
common cold with a vitamin C supplement: a
double-blind,placebo-controlled survey. Adv Ther. 2002
May-Jun;19(3):151-9.
315. Gorton HC, Jarvis K. The effectiveness of vitamin C in
preventing and relieving the symptoms of virus-induced
respiratory infections. Manipulative Physiol Ther. 1999
Oct;22(8):530-3.
316. Johnston CS, Cox SK. Plasma-Saturating intakes of vitamin
C confer maximal antioxidant protection to plasma. J Am Coll
Nutr. 2001 Dec;20(6):623-7.
317. Thompson D, Williams C, McGregor SJ, Nicholas CW, McArdle
F, Jackson MJ, Powell JR. Prolonged vitamin C supplementation
and recovery from demanding exercise. Int J Sport Nutr Exerc
Metab. 2001 Dec;11(4):466-81.
318. Nieman DC, Peters EM, Henson DA, Nevines EI, Thompson MM.
Influence of vitamin C supplementation on cytokine changes
following an ultramarathon. J Interferon Cytokine Res. 2000
Nov;20(11):1029-35.
319. Romieu I, Trenga C. Diet and obstructive lung diseases.
Epidemiol Rev. 2001;23(2):268-87.
320. Jacob RA. Passive smoking induces oxidant damage
preventable by vitamin C. Nutr Rev. 2000 Aug;58(8):239-41.
321. Panda K, Chattopadhyay R, Chattopadhyay DJ, Chatterjee
IB. Vitamin C prevents cigarette smoke-induced oxidative
damage in vivo. Free Radic Biol Med. 2000 Jul 15;29(2):115-24.
322. Zhang J, Ying X, Lu Q, Kallner A, Xiu RJ, Henriksson P,
Bjorkhem I. A single high dose of vitamin C counteracts the
acute negative effect on microcirculation induced by smoking a
cigarette. Microvasc Res. 1999 Nov;58(3):305-11.
323. Gamble J, Grewal PS, Gartside IB. Vitamin C modifies the
cardiovascular and microvascular responses to cigarette smoke
inhalation in man. Clin Sci (Lond). 2000 Apr;98(4):455-60.
324. Rezaian GR, Taheri M, Mozaffari BE, Mosleh AA, Ghalambor
MA. The salutary effects of antioxidant vitamins on the plasma
lipids of healthy middle aged-to-elderly individuals: a
randomized, double-blind, placebo-controlled study. J Med
Liban. 2002 Jan-Apr;50(1-2):10-3.
325. J Dryburgh DR. Vitamin C and chiropractic. Manipulative
Physiol Ther. 1985 Jun;8(2):95-103.
326. Henley S. Women on the pill are opening up a small case
of side effects every morning. Body Forum. 1977 Jan
30;2(7):20.
327. Gorozhanskaia EG, Gromova EG, Sviridova SP. The role of
ascorbic acid in the combined preoperative preparation of
cancer patients. Vopr Onkol. 1989;35(4):436-41.
328. Sukolinskii VN, Morozkina TS. Prevention of postoperative
complications in patients with stomach cancer using an
antioxidant complex. Vopr Onkol. 1989;35(10):1242-5.
329. Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC,
Hofman A, Witteman JC, Breteler MM. Dietary intake of
antioxidants and risk of Alzheimer disease. JAMA. 2002 Jun
26;287(24):3223-9.
330. Masaki KH, Losonczy KG, Izmirlian G, Foley DJ, Ross GW,
Petrovitch H, Havlik R, White LR. Association of vitamin E and
C supplement use with cognitive function and dementia in
elderly men. Neurology. 2000 Mar 28;54(6):1265-72.
331. Grodstein F, Chen J, Willett WC. High-dose antioxidant
supplements and cognitive function in community-dwelling
elderly women. Am J Clin Nutr. 2003 Apr;77(4):975-84.
332. Diet, Nutrition and the Prevention of Chronic Diseases.
WHO Technical Report Series. Report of a Joint WHO/FAO Expert
Consultation. Geneva 2003. p. 81.
333. Parkin DM. Global cancer statistics in the year 2000.
Lancet Oncology, 2001, 2:533-543.
334. Mezquita Raya P, Munoz Torres M, Lopez Rodriguez F,
Martinez Martin N, Conde Valero A, Ortego Centeno N, Gonzalez
Calvin J, Raya Alvarez E, Luna Jd Jde D, Escobar Jimenez F.
Prevalence of vitamin D deficiency in populations at risk for
osteoporosis: impact on bone integrity. Med Clin (Barc). 2002
Jun 22;119(3):85-9.
335. Rodriguez-Martinez MA, Garcia-Cohen EC. Role of Ca(2+)
and vitamin D in the prevention and treatment of osteoporosis.
Pharmacol Ther. 2002 Jan;93(1):37-49.
336. Lilliu H, Pamphile R, Chapuy MC, Schulten J, Arlot M,
Meunier PJ. Calcium-vitamin D3 supplementation is
cost-effective in hip fractures prevention. Maturitas. 2003
Apr 25;44(4):299-305.
337. Pfeiffer. J Bone Min Res. 2000, 15:1113-6.
338. Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral
vitamin D3 (cholecalciferol) supplementation on fractures and
mortality in men and women living in the community: randomised
double blind controlled trial BMJ 2003;326:469-72.
339. Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud
S, Delmas PD, Meunier PJ. Vitamin D3 and calcium to prevent
hip fractures in the elderly women. N Engl J Med. 1992;
327:1637-1642.
340. Dawson-Hughes B., Harris S. S., Krall E. A., Dallal G. E.
Effect of Calcium and Vitamin D Supplementation on Bone
Density in Men and Women 65 Years of Age or Older. N Engl J
Med 1997; 337:670-676.
341. Fardellone P, Sebert JL, Garabedian M, Bellony R, Maamer
M, Agbomson F, Brazie rM. Prevalence and biological
consequences of vitamin D deficiency in elderly
institutionalized subjects. Rev Rhum Engl Ed. 1995
Oct;62(9):576-81.
342. Markestad T. Effect of season and vitamin D
supplementation on plasma concentrations of 25-hydroxyvitamin
D in Norwegian infants. Acta Paediatr Scand. 1983
Nov;72(6):817-21.
343. Zamora SA, Rizzoli R, Belli DC, Slosman DO, Bonjour JP.
Vitamin D supplementation during infancy is associated with
higher bone mineral mass in prepubertal girls. J Clin
Endocrinol Metab. 1999 Dec;84(12):4541-4.
344. Garland CF, Garland FC, Gorham ED. Calcium and vitamin D.
Their potential roles in colon and breast cancer prevention.
Ann N Y Acad Sci. 1999;889:107-19.
345. Peehl DM. Vitamin D and prostate cancer risk. Eur Urol.
1999;35(5-6):392-4.
346. Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen
SM. Intake of vitamin D and risk of type 1 diabetes: a
birth-cohort study. Lancet. 2001 Nov 3;358(9292):1500-3.
347. Munger KL, Zhang SM, O’Reilly E, Hernan MA, Olek MJ,
Willet WC, Ascherio A. Vitamin D intake and incidence of
multiple sclerosis. Neurology. 2004 Jan 13;62(1):60-65.
348. Goldberg P, Fleming MC, Picard EH. Multiple sclerosis:
decreased relapse rate through dietary supplementation with
calcium, magnesium and vitamin D. Med Hypotheses. 1986
Oct;21(2):193-200.
349. Sasidharan PK, Rajeev E, Vijayakumari V. Tuberculosis and
vitamin D deficiency. J Assoc Physicians India. 2002
Apr;50:554-8.
350. Bicknel F, Prescott F. The Vitamins in Medicine, third
edition. Milwaukee, WI: Lee Foundation. 1953, p.544, 584-591.
351. Vieth, R. (1999). Vitamin D supplementation,
25-hydroxyvitamin D concentrations, and safety. American
Journal of Clinical Nutrition, Vol. 69, No. 5, 842-856, May
1999.
352. Marya RK, Rathee S, Lata V, Mudgil S. Effects of vitamin
D supplementation in pregnancy. Gynecol Obstet Invest.
1981;12(3):155-61.
353. Azen SP, Qian D, Mack WJ, et al. Effect of supplementary
antioxidant vitamin intake on carotid arterial wall
intima-media thickness in a controlled clinical trial of
cholesterol lowering. Circulation. 1996;94(10):2369-2372.
354. Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman
K, Mitchinson MJ. Randomised controlled trial of vitamin E in
patients with coronary disease: Cambridge Heart Antioxidant
Study (CHAOS). Lancet. 1996;347(9004):781-786.
355. Boaz M, Smetana S, Weinstein T, et al. Secondary
prevention with antioxidants of cardiovascular disease in
endstage renal disease (SPACE): randomised placebo-controlled
trial. Lancet. 2000;356(9237):1213-1218.
356. Williams SR. Nutrition and Diet Therapy, Seventh Edition.
St. Louis: Mosby, 1993. (p 186). Sixth edition, 1989. (p 225).
357. Williams HTG, Fenna D, MacBeth RA. Alpha Tocopherol in
the Treatment of Intermittent Claudication. Surgery,
Gynecology and Obstetrics 132:#4, 662-666, April 1971.
358. Vasdev S, Gill V, Parai S, Longerich L, Gadag V. Dietary
vitamin E supplementation lowers blood pressure in
spontaneously hypertensive rats. Mol Cell Biochem. 2002 Sep;
238(1-2):111-7.
359. Vaziri ND, Ni Z, Oveisi F, Liang K, Pandian R. Enhanced
nitric oxide inactivation and protein nitration by reactive
oxygen species in renal insufficiency. Hypertension. 2002 Jan;
39(1):135-41.
361. Shute, Vogelsang, Skelton and Shute. Surg., Gyn. and
Obst. 86:1. 1948.
362. Malmberg KJ, Lenkei R, Petersson M, Ohlum T, Ichihara F,
Glimelius B, Frodin JE, Masucci G, Kiessling R. A short-term
dietary supplementation of high doses of vitamin E increases T
helper 1 cytokine production in patients with advanced
colorectal cancer. Clin Cancer Res. 2002 Jun; 8(6):1772-8.
363. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K,
Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E,
Schneider LS, Thal LJ. A controlled trial of selegiline,
alpha-tocopherol, or both as treatment for Alzheimer's
disease. The Alzheimer's Disease Cooperative Study. N Engl J
Med. Apr 24; 336(17):1216-22. 1997.
364. Ogunmekan AO, Hwang PA. A randomized, double-blind,
placebo-controlled, clinical trial of D-alpha-tocopheryl
acetate (vitamin E), as add-on therapy, for epilepsy in
children. Epilepsia. 1989 Jan-Feb; 30(1):84-9.
365. Hittner HM, Godio LB, Rudolph AJ, Adams JM, Garcia-Prats
JA, Friedman Z, Kautz JA, Monaco WA. Retrolental fibroplasia:
efficacy of vitamin E in a double-blind clinical study of
preterm infants. N Engl J Med. 1981 Dec 3; 305(23):1365-71.
366. Cheraskin E. Antioxidants in health and disease: the big
picture. Journal of Orthomolecular Medicine 10: #2, 89-96,
Second Quarter, 1995, citing Meydani, S.N., Barklund, M.P.,
Liu, S., Meydani, M., Miller, R.A., Cannon, J.G., Morrow,
F.D., Rocklin, R., Blumberg, J.B. Effect of Vitamin E
Supplementation on Immune Responsiveness of Healthy Elderly
Subjects. FASEB Journal 3: A1057, 1989.
367. Meydani, S.N., Barkiund, M.P., Liu, S., Meydani, M.,
Miller, R.A., Cannon, J.G., Morrow, F.D., Rocklin, R.,
Blumberg, J.B. Vitamin E supplementation enhances
cell-mediated immunity in healthy elderly subjects. American
Journal of Clinical Nutrition 52:#3, 557-563, September 1990.
368. British Medical Journal, i, 890, 1940 (cited in Bicknell
& Prescott. The vitamins in medicine. Milwaukee: Lee
Foundation, 1953, p 632).
369. Mecocci P, Polidori MC, Troiano L, Cherubini A, Cecchetti
R, Pini G, Straatman M, Monti D, Stahl W, Sies H, Franceschi
C, Senin U. Plasma antioxidants and longevity: a study on
healthy centenarians. Free Radic Biol Med. 2000 Apr
15;28(8):1243-8.
370. Binkley NC, Krueger DC, Kawahara TN, Engelke JA, Chappell
RJ, Suttie JW. A high phylloquinone intake is required to
achieve maximal osteocalcin gamma-carboxylation. Am J Clin
Nutr. 2002 Nov;76(5):1055-60.
371. Ferland G, Sadowski JA, O'Brien ME. Dietary induced
subclinical vitamin K deficiency in normal human subjects. J
Clin Invest. 1993 Apr;91(4):1761-8.
372. Bugel S. Vitamin K and bone health. Proc Nutr Soc. 2003
Nov;62(4):839-43.
373. Feskanich D, Weber P, Willett WC, Rockett H, Booth SL,
Colditz GA. Vitamin K intake and hip fractures in women: a
prospective study. Am J Clin Nutr. 1999;69(1):74-79.
374. Booth SL, Tucker KL, Chen H, et al. Dietary vitamin K
intakes are associated with hip fracture but not with bone
mineral density in elderly men and women. Am J Clin Nutr.
2000;71(5):1201-1208.
375. Feskanich D, Weber P, Willett WC, Rockett H, Booth SL,
Colditz GA. Vitamin K intake and hip fractures in women: a
prospective study. Am J Clin Nutr. 1999 Jan;69(1):74-9.
376. Booth SL, Broe KE, Gagnon DR, Tucker KL, Hannan MT,
McLean RR, Dawson-Hughes B, Wilson PW, Cupples LA, Kiel DP.
Vitamin K intake and bone mineral density in women and men. Am
J Clin Nutr. 2003 Feb;77(2):512-6.
377. Weber P. Management of osteoporosis: is there a role for
vitamin K? Int J Vitam Nutr Res. 1997;67(5):350-6.
378. Ozuru R, Sugimoto T, Yamaguchi T, Chihara K.
Time-dependent effects of vitamin K2 (menatetrenone) on bone
metabolism in postmenopausal women. Endocr J. 2002
Jun;49(3):363-70.
379. Ushiroyama T, Ikeda A, Ueki M. Effect of continuous
combined therapy with vitamin K(2) and vitamin D(3) on bone
mineral density and coagulofibrinolysis function in
postmenopausal women. Maturitas. 2002 Mar 25;41(3):211-21.
380. Iwamoto J, Takeda T, Ichimura S. Effect of combined
administration of vitamin D3 and vitamin K2 on bone mineral
density of the lumbar spine in postmenopausal women with
osteoporosis. J Orthop Sci. 2000;5(6):546-51.
381. Iketani T, Kiriike N, Murray, Stein B, Nagao K, Nagata T,
Minamikawa N, Shidao A, Fukuhara H. Effect of menatetrenone
(vitamin K2) treatment on bone loss in patients with anorexia
nervosa. Psychiatry Res. 2003 Mar 25;117(3):259-69.
382. Sato Y, Honda Y, Kaji M, Asoh T, Hosokawa K, Kondo I,
Satoh K. Amelioration of osteoporosis by menatetrenone in
elderly female Parkinson's disease patients with vitamin D
deficiency. Bone. 2002 Jul;31(1):114-8.
383. Durie PR. Vitamin K and the management of patients with
cystic fibrosis. CMAJ. 1994 Oct 1;151(7):933-6.
384. Schoon EJ, Muller MC, Vermeer C, Schurgers LJ, Brummer
RJ, Stockbrugger RW. Low serum and bone vitamin K status in
patients with longstanding Crohn's disease: another
pathogenetic factor of osteoporosis in Crohn's disease? Gut.
2001 Apr;48(4):473-7.
385. Malik S, Udani RH, Bichile SK, Agrawal RM, Bahrainwala
AT, Tilaye S. Comparative study of oral versus injectable
vitamin K in neonates. Indian Pediatr. 1992 Jul;29(7):857-9.
386. Isarangkura PB, Bintadish P, Tejavej A, Siripoonya P,
Chulajata R, Green GM, Chalermchandra K. Vitamin K prophylaxis
in the neonate by the oral route and its significance in
reducing infant mortality and morbidity. J Med Assoc Thai.
1986 Oct;69 Suppl 2:56-61.
387. Olson JA. Recommended dietary intakes (RDI) of vitamin K
in humans. Am J Clin Nutr. 1987 Apr;45(4):687-92.
388. Nishiguchi T, Yamashita M, Maeda M, Matsuyama K,
Kobayashi T, Kanayama N, Terao T. Improvement of vitamin K
status of breastfeeding infants with maternal supplement of
vitamin K2 (MK40). Semin Thromb Hemost. 2002 Dec;28(6):533-8.
389. Jie KS, Bots ML, Vermeer C, Witteman JC, Grobbee DE.
Vitamin K intake and osteocalcin levels in women with and
without aortic atherosclerosis: a population-based study.
Atherosclerosis. 1995;116(1):117-123.
390. Sakamoto N, Nishiike T, Iguchi H, Sakamoto K.
Relationship between acute insulin response and vitamin K
intake in healthy young male volunteers. Diabetes Nutr Metab.
1999 Feb;12(1):37-41.
391. Dietary Reference Intakes for Calcium, Phosphorous,
Magnesium, Vitamin D, and Fluoride (1997).
392. Kaufman JM. Role of calcium and vitamin D in the
prevention and the treatment of postmenopausal osteoporosis:
an overview. Clin Rheumatol. 1995 Sep;14 Suppl 3:9-13.
393. Ma J, Betts NM. Zinc and copper intakes and their major
food sources for older adults in the 1994-96 continuing survey
of food intakes by individuals (CSFII). J Nutr. 2000
Nov;130(11):2838-43.
394. Swerts J, Benemariya H, Robberecht H, van Cauwenbergh R,
Deelstra H. Daily dietary intake of copper and zinc by several
population groups in Belgium: preliminary reports. J Trace
Elem Electrolytes Health Dis. 1993 Sep;7(3):165-9.
395. Thomas AJ, Bunker VW, Hinks LJ, Sodha N, Mullee MA,
Clayton BE. Energy, protein, zinc and copper status of
twenty-one elderly inpatients: analysed dietary intake and
biochemical indices. Br J Nutr. 1988 Mar;59(2):181-91.
396. Failla ML. Considerations for determining 'optimal
nutrition' for copper, zinc, manganese and molybdenum. Proc
Nutr Soc. 1999 May;58(2):497-505.
397. Williams DM. Copper deficiency in humans. Semin Hematol.
1983 Apr;20(2):118-28.
398. Holden JM, Wolf WR, Mertz W. Zinc and copper in
self-selected diets. J Am Diet Assoc. 1979 Jul;75(1):23-8.
399. Alarcon OM, Guerrero Y, Ramirez de Fernandez M, D'Jesus
I, Burguera M, Burguera JL, Di Bernardo ML. Effect of copper
supplementation on blood pressure values in patients with
stable moderate hypertension. Arch Latinoam Nutr. 2003
Sep;53(3):271-6.
400. Milne DB, Nielsen FH. Effects of a diet low in copper on
copper-status indicators in postmenopausal women. Am J Clin
Nutr. 1996 Mar;63(3):358-64.
401. Milne DB. Copper intake and assessment of copper status.
Am J Clin Nutr. 1998 May;67(5 Suppl):1041S-1045S.
402. Aggett PJ. An overview of the metabolism of copper. Eur J
Med Res. 1999 Jun 28;4(6):214-6.
403. Klevay LM. Lack of a recommended dietary allowance for
copper may be hazardous to your health. J Am Coll Nutr. 1998
Aug;17(4):322-6.
404. Davydenko NV, Smirnova IP, Kvasha EA, Gorbas' IM. The
relationship between the copper and zinc intake with food and
the prevalence of ischemic heart disease and its risk factors.
Lik Sprava. 1995 May-Jun;(5-6):73-7.
405. Saari JT, Schuschke DA. Cardiovascular effects of dietary
copper deficiency. Biofactors. 1999;10(4):359-75.
406. Klevay LM. Ischemic heart disease. A major obstacle to
becoming old. Clin Geriatr Med. 1987 May;3(2):361-72.
407. Klevay LM. Cardiovascular disease from copper
deficiency--a history. J Nutr. 2000 Feb;130(2S
Suppl):489S-492S.
408. Chandra RK. Grace A. Goldsmith Award lecture. Trace
element regulation of immunity and infection. J Am Coll Nutr.
1985;4(1):5-16.
409. Anderson RA. Chromium as an essential nutrient for
humans. Regul Toxicol Pharmacol. 1997 Aug;26(1 Pt 2):S35-41.
410. Anderson RA. Chromium in the prevention and control of
diabetes. Diabetes Metab. 2000 Feb;26(1):22-7.
411. Preuss HG, Anderson RA. Chromium update: examining recent
literature 1997-1998. Curr Opin Clin Nutr Metab Care. 1998
Nov;1(6):509-12.
412. Anderson RA. Chromium metabolism and its role in disease
processes in man. Clin Physiol Biochem. 1986;4(1):31-41.
414. Ravina A, Slezack L. Chromium in the treatment of
clinical diabetes mellitus. Harefuah. 1993 Sep;125(5-6):142-5,
191.
415. Ghosh D, Bhattacharya B, Mukherjee B, Manna B, Sinha M,
Chowdhury J, Chowdhury S. Role of chromium supplementation in
Indians with type 2 diabetes mellitus. J Nutr Biochem. 2002
Nov;13(11):690-697.
416. Ryan GJ, Wanko NS, Redman AR, Cook CB. Chromium as
adjunctive treatment for type 2 diabetes. Ann Pharmacother.
2003 Jun;37(6):876-85.
417. Morris BW, Kouta S, Robinson R, MacNeil S, Heller S.
Chromium supplementation improves insulin resistance in
patients with Type 2 diabetes mellitus. Diabet Med. 2000
Sep;17(9):684-5.
418. Bahijiri SM, Mira SA, Mufti AM, Ajabnoor MA. The effects
of inorganic chromium and brewer's yeast supplementation on
glucose tolerance, serum lipids and drug dosage in individuals
with type 2 diabetes. Saudi Med J. 2000 Sep;21(9):831-7.
419. Anderson RA, Cheng N, Bryden NA, Polansky MM, Cheng N,
Chi J, Feng J.
Elevated intakes of supplemental chromium improve glucose and
insulin variables in individuals with type 2 diabetes.
Diabetes. 1997 Nov;46(11):1786-91.
420. Anderson RA. Chromium, glucose intolerance and diabetes.
J Am Coll Nutr. 1998 Dec;17(6):548-55.
421. Anderson RA. Trace elements and cardiovascular diseases.
Acta Pharmacol Toxicol (Copenh). 1986;59 Suppl 7:317-24.
422. Mossop RT. Trivalent chromium, in atherosclerosis and
diabetes. Cent Afr J Med. 1991 Nov;37(11):369-74.
423. Simonoff M. Chromium deficiency and cardiovascular risk.
Cardiovasc Res. 1984 Oct;18(10):591-6.
424. Hansson L, Huunan-Seppala A, Mattila A. The content of
calcium, magnesium, copper, zinc, lead and chromium in the
blood of patients with rheumatoid arthritis. Scand J
Rheumatol. 1975;4(1):33-8.
425. Davidson JR, Abraham K, Connor KM, McLeod MN.
Effectiveness of chromium in atypical depression: a
placebo-controlled trial. Biol Psychiatry. 2003 Feb
1;53(3):261-4.
426. Bahadori B, Wallner S, Schneider H, Wascher TC, Toplak H.
Effect of chromium yeast and chromium picolinate on body
composition of obese, non-diabetic patients during and after a
formula diet. Acta Med Austriaca. 1997;24(5):185-7.
427. Crawford V, Scheckenbach R, Preuss HG. Effects of
niacin-bound chromium supplementation on body composition in
overweight African-American women. Diabetes Obes Metab. 1999
Nov;1(6):331-7.
428. Lamson DS, Plaza SM. The safety and efficacy of high-dose
chromium. Altern Med Rev. 2002 Jun;7(3):218-35.
429. Dietary Reference Intakes for Vitamin A, Vitamin K,
Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese,
Molybdenum, Nickel, Silicon, Vanadium, and Zinc (2001). US
National Academy of Science.
430. Dietary Reference Intakes for Vitamin A, Vitamin K,
Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese,
Molybdenum, Nickel, Silicon, Vanadium, and Zinc (2001). US
National Academy of Science.
431. Magnesium Trace Elements 10: 162-28, 1997.
432. Sjogren, A., Edvinsson, L., and Fallgren, B. Magnesium
deficiency in coronary artery disease and cardiac arrhythmias.
J Int Med, 1989;226:213-22.
433. Dubey, A., and Solomon, R. Magnesium, Myocardial
ischaemia and arrhythmias. The role of magnesium in myocardial
infarction. Drugs, 1989;37:1-7.
434. Altura B. Magnesium in cardiovascular biology. Scientific
American May/June 1995;28-35.
435. Turner RE, Langkamp-Henken B, Littell RC, Lukowski MJ,
Suarez MF. Comparing nutrient intake from food to the
estimated average requirements shows middle- to upper-income
pregnant women lack iron and possibly magnesium. J Am Diet
Assoc. 2003 Apr;103(4):461-6.
436. Vaquero MP. Magnesium and trace elements in the elderly:
intake, status and recommendations. J Nutr Health Aging.
2002;6(2):147-53.
437. van der Sijs IH, Ho-Dac-Pannekeet MM. The treatment of
hypomagnesemia. Ned Tijdschr Geneeskd. 2002 May
18;146(20):934-8.
438. Milionis HJ, Alexandrides GE, Liberopoulos EN, Bairaktari
ET, Goudevenos J, Elisaf MS. Hypomagnesemia and concurrent
acid-base and electrolyte abnormalities in patients with
congestive heart failure. Eur J Heart Fail. 2002
Mar;4(2):167-73.
439. Schimatschek HF, Rempis R. Prevalence of hypomagnesemia
in an unselected German population of 16,000 individuals.
Magnes Res. 2001 Dec;14(4):283-90.
440. Iannello S, Belfiore F. Hypomagnesemia. A review of
pathophysiological, clinical and therapeutical aspects.
Panminerva Med. 2001 Sep;43(3):177-209.
441. Deshmukh CT, Rane SA, Gurav MN. Hypomagnesaemia in
paediatric population in an intensive care unit. J Postgrad
Med. 2000 Jul-Sep;46(3):179-80.
442. Verive MJ, Irazuzta J, Steinhart CM, Orlowski JP,
Jaimovich DG. Evaluating the frequency rate of hypomagnesemia
in critically ill pediatric patients by using multiple
regression analysis and a computer-based neural network. Crit
Care Med. 2000 Oct;28(10):3534-9.
443. Fox CH, Ramsoomair D, Mahoney MC, Carter C, Young B,
Graham R. An investigation of hypomagnesemia among ambulatory
urban African Americans. J Fam Pract. 1999 Aug;48(8):636-9.
444. Faintuch JJ, Menezes MS. Magnesium and myocardial
infarction. Brazilian aspects. Rev Hosp Clin Fac Med Sao
Paulo. 1997 Nov-Dec;52(6):333-6.
445. Durlach J, Bac P, Durlach V, Rayssiguier Y, Bara M,
Guiet-Bara A. Magnesium status and ageing: an update. Magnes
Res. 1998 Mar;11(1):25-42.
446. Durlach J, Bac P, Durlach V, Durlach A, Bara M,
Guiet-Bara A. Are age-related neurodegenerative diseases
linked with various types of magnesium depletion? Magnes Res.
1997 Dec;10(4):339-53.
447. Singh RB, Rastogi V, Singh R, Niaz MA, Srivastav S, Aslam
M, Singh NK, Moshir M, Postiglione A. Magnesium and
antioxidant vitamin status and risk of complications of ageing
in an elderly urban population. Magnes Res. 1996
Dec;9(4):299-306.
448. Singh RB, Rastogi V, Niaz MA, Sharma JP, Raghuvanshi R,
Moshira M. Epidemiological study of magnesium status and risk
of hypertension in a rural population of north India. Magnes
Res. 1996 Oct;9(3):173-81.
449. Singh RB, Niaz MA, Ghosh S, Rastogi V, Raghuvanshi RS,
Moshiri M. Epidemiological study of magnesium status and risk
of coronary artery disease in elderly rural and urban
populations of north India. Magnes Res. 1996 Oct;9(3):165-72.
450. Bondarev GI, Feoktistova AI, Zemlianskaia TA. Nutritional
status of native and non-native population of Russia's Extreme
North and Far East. Vopr Pitan. 1993 Mar-Apr;(2):14-8.
451. Davydenko NV, Vasilenko IG. Magnesium level in food
rations and the prevalence of ischemic heart disease among the
population. Gig Sanit. 1991 May;(5):44-6.
452. Touitou Y, Godard JP, Ferment O, Chastang C, Proust J,
Bogdan A, Auzeby A, Touitou C. Prevalence of magnesium and
potassium deficiencies in the elderly. Clin Chem. 1987
Apr;33(4):518-23.
453. Elin RJ. Magnesium metabolism in health and disease. Dis
Mon. 1988 Apr;34(4):161-218.
454. Landon RA, Young EA. Role of magnesium in regulation of
lung function. J Am Diet Assoc. 1993 Jun;93(6):674-7.
455. Rubeiz GJ, Thill-Baharozian M, Hardie D, Carlson RW.
Association of hypomagnesemia and mortality in acutely ill
medical patients. Crit Care Med. 1993 Feb;21(2):203-9.
456. Sherwood RA, Rocks BF, Stewart A, Saxton RS. Magnesium
and the premenstrual syndrome. Ann Clin Biochem. 1986 Nov;23 (
Pt 6):667-70.
457. Posaci C, Erten O, Uren A, Acar B. Plasma copper, zinc
and magnesium levels in patients with premenstrual tension
syndrome. Acta Obstet Gynecol Scand. 1994 Jul;73(6):452-5.
458. Britton J, Pavord I, Richards K, Wisniewski A, Knox A,
Lewis S, Tattersfield A, Weiss S. Dietary magnesium, lung
function, wheezing, and airway hyperreactivity in a random
adult population sample. Lancet. 1994 Aug 6;344(8919):357-62.
459. Steidl L, Ditmar R. Blood magnesium findings in
osteoporosis. Acta Univ Palacki Olomuc Fac Med.
1990;126:117-28.
460. Cohen L. Recent data on magnesium and osteoporosis.
Magnes Res. 1988 Jul;1(1-2):85-7.
461. Driessens FC. Prevention of osteoporosis and pathological
calcification. Ned Tijdschr Tandheelkd. 1993 Sep;100(9):412,
413-4.
462. Walti MK, Zimmermann MB, Spinas GA, Hurrell RF. Low
plasma magnesium in type 2 diabetes. Swiss Med Wkly. 2003 May
17;133(19-20):289-92.
463. Djurhuus MS, Klitgaard NA, Pedersen KK, Blaabjerg O,
Altura BM, Altura BT, Henriksen JE. Magnesium reduces
insulin-stimulated glucose uptake and serum lipid
concentrations in type 1 diabetes. Metabolism. 2001
Dec;50(12):1409-17.
464. Naghii MR, Samman S. The role of boron in nutrition and
metabolism. Prog Food Nutr Sci. 1993 Oct-Dec;17(4):331-49.
465. Devirian TA, Volpe SL. The physiological effects of
dietary boron. Crit Rev Food Sci Nutr. 2003;43(2):219-31.
466. Nielsen FH, Hunt CD, Mullen LM, Hunt JR. Effect of
dietary boron on mineral, estrogen, and testosterone
metabolism in postmenopausal women. FASEB J. 1987
Nov;1(5):394-7.
467. Nielsen FH. Studies on the relationship between boron and
magnesium which possibly affects the formation and maintenance
of bones. Magnes Trace Elem. 1990;9(2):61-9.
468. Naghii MR, Samman S. The effect of boron supplementation
on its urinary excretion and selected cardiovascular risk
factors in healthy male subjects. Biol Trace Elem Res. 1997
Mar;56(3):273-86.
469. Penland JG. Dietary boron, brain function, and cognitive
performance. Environ Health Perspect. 1994 Nov;102 Suppl
7:65-72.
470. Newnham RE. Essentiality of boron for healthy bones and
joints. Environ Health Perspect. 1994 Nov;102 Suppl 7:83-5.
471. Zhang Z-F, Winton MI, Rainey C, et al: Boron is
associated with decreased risk of human prostate cancer. FASEB
J 15:A1089, 2001.
472. Feskanich D, Willett WC, Stampfer MJ, Colditz GA. Protein
consumption and bone fractures in women. Am J Epidemiol
1996;143:472–9.
473. Raloff J. Reasons for boning up on manganese. Science
News 1986;Sep 27:199 [review].
474. Gold M. Basketball bones. Science 1980;80:101–2.
475. Strause L, Saltman P, Smith KT, et al. Spinal bone loss
in postmenopausal women supplemented with calcium and trace
minerals. J Nutr 1994;124:1060–4.
476. Kosenko LG. Concentration of trace elements in the blood
of patients with diabetes mellitus. Fed Proc Transl (Suppl)
1965;24:237–8.
477. Baly DL, Schneiderman JS, Garcia-Welsh AL. Effect of
manganese deficiency on insulin binding, glucose transport and
metabolism in rat adipocytes. J Nutr 1990;120:1075–9.
478. Kunin RA. Manganese in dyskinesias. Am J Psychiatry
1976;133:105.
479. Norris JP, Sams RE. More on the use of manganese in
dyskinesia. Am J Psychiatry 1997;134:1448.
480. Hoffer A. Tardive dyskinesia treated with manganese. Can
Med Assoc J 1977;117:859.
481. Balch and Balch, Prescription for Nutritional Healing, p
239-240.
482. Kimura M, Itokawa Y. Cooking losses of minerals in foods
and its nutritional significance. J Nutr Sci Vitaminol (Tokyo)
1990;36:S25–33.
483. Pennington JAT. Bowes and Church’s Food Values of
Portions Commonly Used, 17th ed. Philadelphia, PA: Lippincott
Williams & Wilkins, 1997.
484. Davis CD, Malecki EA, Gerger JL. Interactions among
dietary manganese, heme iron, and nonheme iron in women. Am J
Clin Nutr 1992;56:926–32.
487. Kibblewhite MG, Van Rensburg SJ, Laker MC, Rose EF.
Evidence for an intimate geochemical factor in the etiology of
esophageal cancer. Environ Res. 1984 Apr;33(2):370-8.
488. Tuyns AJ, Pequignot G, Jensen OM. Nutrition, alcohol and
oesophageal cancer. Bull Cancer. 1978;65(1):58-64.
489. Nakadaira H, Endoh K, Yamamoto M, Katoh K. Distribution
of selenium and molybdenum and cancer mortality in Niigata,
Japan. Arch Environ Health. 1995 Sep-Oct;50(5):374-80.
490. Johnson JL, Wuebbens MM, Mandell R, Shih VE. Molybdenum
cofactor deficiency in a patient previously characterized as
deficient in sulfite oxidase. Biochem Med Metabol Biol
1988;40:86–93.
491. Moss M. Effects of molybdenum on pain and general health:
a pilot study. J Nutr Environ Med 1995;5:55–61.
492. Yao ZM, Zhang LH. Microelement-molybdenum and its use for
the treatment of children's fluorine-stained teeth. Zhonghua
Yu Fang Yi Xue Za Zhi. 1992 Jan;26(1):28-31.
493. Murphy J, Hannon EM, Kiely M, Flynn A, Cashman KD.
Selenium intakes in 18-64-y-old Irish adults. Eur J Clin Nutr.
2002 May;56(5):402-8.
494. Tutel'ian VA, Khotimchenko SA. Selenium as an essential
and deficient factor in the nutrition of Russian population.
Vestn Ross Akad Med Nauk. 2001;(6):31-4.
495. Kvicala J, Zamrazil V, Jiranek V. Characterization of
selenium status of inhabitants in the region Usti nad Orlici,
Czech Republic by INAA of blood serum and hair and
fluorimetric analysis of urine. Biol Trace Elem Res. 1999
Winter;71-72:31-9.
496. Kvicala J, Zamrazil V, Cerovska J, Bednar J, Janda J.
Evaluation of selenium supply and status of inhabitants in
three selected rural and urban regions of the Czech Republic.
Biol Trace Elem Res. 1995 Jan-Mar;47(1-3):365-75.
497. Bogye G, Feher J, Georg A, Antti A. Relationship between
selenium deficiency and high mortality and morbidity of
cardiovascular diseases. Orv Hetil. 1994 Jan 16;135(3):115-8.
498. Sluis KB, Darlow BA, George PM, Mogridge N, Dolamore BA,
Winterbourn CC. Selenium and glutathione peroxidase levels in
premature infants in a low selenium community (Christchurch,
New Zealand). Pediatr Res. 1992 Aug;32(2):189-94.
499. Maksimovic ZJ, Djujic I, Jovic V, Rsumovic M. Selenium
deficiency in Yugoslavia. Biol Trace Elem Res. 1992
Apr-Jun;33:187-96.
500. Kivela SL, Maenpaa P, Nissinen A, Alfthan G, Punsar S,
Enlund H, Puska P. Vitamin A, vitamin E and selenium status in
an aged Finnish male population. Int J Vitam Nutr Res.
1989;59(4):373-80.
501. Wasowicz W, Zachara BA. Selenium concentrations in the
blood and urine of a healthy Polish sub-population. J Clin
Chem Clin Biochem. 1987 Jul;25(7):409-12.
502. Maksimovic Z, Djujic I. Selenium research in Serbia,
Yugoslavia. J Environ Pathol Toxicol Oncol.
1998;17(3-4):165-71.
503. Kim YS, Milner J. Molecular targets for selenium in
cancer prevention. Nutr Cancer. 2001;40(1):50-4.
504. Yu, Shu-Yu et al. Regional variation of cancer mortality
incidence and its relation to selenium levels in China. Biol.
Trace Elem res. 7:21-29, 1985.
505. Burguera JL, Burguera M, Gallignani M, Alarcon OM,
Burguera JA. Blood serum selenium in the province of Merida,
Venezuela, related to sex, cancer incidence and soil selenium
content. J Trace Elem Electrolytes Health Dis 1990
Jun;4(2):73-7.
506. Schrauzer GN. Bioinorg Chem 1976;5(3):275-81. Selenium
and cancer: a review.
507. Shamberger RJ, Frost DV. Possible protective effect of
selenium against human cancer. Can Med Assoc J. 1969 Apr
12;100(14):682.
508. Shamberger, R. J., and C. E. Willis. 1971. Selenium
distribution and human cancer mortality. CRC Crit. Rev. Clin.
Lab. Sci. 2:211-221.
509. Shamberger, R. J., S. A. Tytko, and C. E. Willis. 1976.
Antioxidants and cancer. Part VI. Selenium and age-adjusted
human cancer mortality. Arch. Environ. Health 31:231-235.
510. Clark LC. The epidemiology of selenium and cancer. Fed
Proc 1985 Jun;44(9):2584-9.
511. Shrauzer GN, White DA, Schneider CJ. Bioinorg Chem
1977;7(1):23-31 Cancer mortality correlation studies--III:
statistical associations with dietary selenium intakes.
512. Duffield-Lillico AJ, Reid ME, Turnbull BW, Combs GF Jr,
Slate EH, Fischbach LA, Marshall JR, Clark LC. Baseline
characteristics and the effect of selenium supplementation on
cancer incidence in a randomized clinical trial: a summary
report of the Nutritional Prevention of Cancer Trial. Cancer
Epidemiol Biomarkers Prev. 2002 Jul;11(7):630-9.
513. Combs GF Jr, Clark LC, Turnbull BW. Reduction of cancer
mortality and incidence by selenium supplementation. Med Klin
(Munich). 1997 Sep 15;92 Suppl 3:42-5.
514. Li WG. Preliminary observations on effect of selenium
yeast on high risk populations with primary liver cancer.
Zhonghua Yu Fang Yi Xue Za Zhi. 1992 Sep;26(5):268-71.
515. Helzlsouer KJ, Huang HY, Alberg AJ, Hoffman S, Burke A,
Norkus EP, Morris JS, Comstock GW. Association between
alpha-tocopherol, gamma-tocopherol, selenium, and subsequent
prostate cancer. J Natl Cancer Inst. 2000 Dec
20;92(24):2018-23.
516. Nelson MA, Porterfield BW, Jacobs ET, Clark LC. Selenium
and prostate cancer prevention. Semin Urol Oncol. 1999
May;17(2):91-6.
517. Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK,
Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A,
Lesher JL Jr, Park HK, Sanders BB Jr, Smith CL, Taylor JR.
Effects of selenium supplementation for cancer prevention in
patients with carcinoma of the skin. A randomized controlled
trial. Nutritional Prevention of Cancer Study Group. JAMA.
1996;276:1957-1963.
518. Moore JA, Noiva R, Wells IC. Selenium concentrations in
plasma of patients with arteriographically defined coronary
atherosclerosis. Clin Chem. 1984 Jul;30(7):1171-3.
519. Oster O, Drexler M, Schenk J, Meinertz T, Kasper W,
Schuster CJ, Prellwitz W. The serum selenium concentration of
patients with acute myocardial infarction. Ann Clin Res.
1986;18(1):36-42.
520. Kok FJ, Hofman A, Witteman JC, de Bruijn AM, Kruyssen DH,
de Bruin M, Valkenburg HA. Decreased selenium levels in acute
myocardial infarction. JAMA. 1989 Feb 24;261(8):1161-4.
521. Salonen JT, Alfthan G, Huttunen JK, Pikkarainen J, Puska
P. Association between cardiovascular death and myocardial
infarction and serum selenium in a matched-pair longitudinal
study. Lancet. 1982 Jul 24;2(8291):175-9.
522. Cowgill UM. The distribution of selenium and mortality
owing to acquired immune deficiency syndrome in the
continental United States. Biol Trace Elem Res. 1997
Jan;56(1):43-61.
523. Burbano X, Miguez-Burbano MJ, McCollister K, Zhang G,
Rodriguez A, Ruiz P, Lecusay R, Shor-Posner G. Impact of a
selenium chemoprevention clinical trial on hospital admissions
of HIV-infected participants. HIV Clin Trials. 2002
Nov-Dec;3(6):483-91.
524. Borner J, Zimmermann T, Albrecht S, Roesner D. Selenium
administration in children with SIRS. Med Klin (Munich). 1999
Oct 15;94 Suppl 3:93-6.
525. Bowrey DJ, Morris-Stiff GJ, Puntis MC. Selenium
deficiency and chronic pancreatitis: disease mechanism and
potential for therapy. HPB Surg. 1999;11(4):207-15; discussion
215-6.
526. Kurihara M, Kumagai K, Nakae Y, Nishino I, Nonaka I. Two
sibling patients with non-Fukuyama type congenital muscular
dystrophy with low serum selenium levels--therapeutic effects
of oral selenium administration. No To Hattatsu. 2000
Jul;32(4):346-51.
527. Gazdik F, Horvathova M, Gazdikova K, Jahnova E. The
influence of selenium supplementation on the immunity of
corticoid-dependent asthmatics. Bratisl Lek Listy.
2002;103(1):17-21.
528. Bonomini M, Forster S, De Risio F, Rychly J, Nebe B,
Manfrini V, Klinkmann H, Albertazzi A. Effects of selenium
supplementation on immune parameters in chronic uraemic
patients on haemodialysis. Nephrol Dial Transplant.
1995;10(9):1654-61.
529. Aydin K, Kendirci M, Kurtoglu S, Karakucuk EI, Kiris A.
Iodine and selenium deficiency in school-children in an
endemic goiter area in Turkey. J Pediatr Endocrinol Metab.
2002 Jul-Aug;15(7):1027-31.
530. Keskes-Ammar L, Feki-Chakroun N, Rebai T, Sahnoun Z,
Ghozzi H, Hammami S, Zghal K, Fki H, Damak J, Bahloul A. Sperm
oxidative stress and the effect of an oral vitamin E and
selenium supplement on semen quality in infertile men. Arch
Androl. 2003 Mar-Apr;49(2):83-94.
531. Scott R, MacPherson A, Yates RW, Hussain B, Dixon J. The
effect of oral selenium supplementation on human sperm
motility. Br J Urol. 1998 Jul;82(1):76-80.
532. Benton D, Cook R. The impact of selenium supplementation
on mood. Biol Psychiatry. 1991 Jun 1;29(11):1092-8.
533. Benton D, Cook R. Selenium supplementation improves mood
in a double-blind crossover trial. Psychopharmacology (Berl).
1990;102(4):549-50.
534. Foster HD, Zhang L. Longevity and selenium deficiency:
evidence from the People's Republic of China. Sci Total
Environ. 1995 Aug 18;170(1-2):133-9.
535. Laryea MD, Schnittert B, Kersting M, Wilhelm M, Lombeck
I. Macronutrient, copper, and zinc intakes of young German
children as determined by duplicate food samples and diet
records. Ann Nutr Metab. 1995;39(5):271-8.
536. Worwag M, Classen HG, Schumacher E. Prevalence of
magnesium and zinc deficiencies in nursing home residents in
Germany. Magnes Res. 1999 Sep;12(3):181-9.
537. Olivares M, Pizarro F, de Pablo S, Araya M, Uauy R. Iron,
zinc, and copper: contents in common Chilean foods and daily
intakes in Santiago, Chile. Nutrition. 2004 Feb;20(2):205-12.
538. Prasad AS. Zinc deficiency in women, infants and
children. J Am Coll Nutr. 1996 Apr;15(2):113-20.
539. Hambidge KM. Zinc deficiency in man: its origins and
effects. Philos Trans R Soc Lond B Biol Sci. 1981 Aug
14;294(1071):129-44.
540. Lemasters GK. Zinc insufficiency during pregnancy. A
review. JOGN Nurs. 1981 Mar-Apr;10(2):124-5. (396).
541. Anetor JI, Senjobi A, Ajose OA, Agbedana EO. Decreased
serum magnesium and zinc levels: atherogenic implications in
type-2 diabetes mellitus in Nigerians. Nutr Health.
2002;16(4):291-300.
543. Wellinghausen N, Kern WV, Jochle W, Kern P. Zinc serum
level in human immunodeficiency virus-infected patients in
relation to immunological status. Biol Trace Elem Res 2000
Feb;73(2):139-49.
544. Baum MK, Campa A, Lai S, Lai H, Page JB. Zinc status in
human immunodeficiency virus type 1 infection and illicit drug
use. Clin Infect Dis. 2003;37 Suppl 2:S117-23.
545. Bergomi M, Rovesti S, Vinceti M, Vivoli R, Caselgrandi E,
Vivoli G. . Zinc and copper status and blood pressure. J Trace
Elem Med Biol. 1997 Nov;11(3):166-9.
546. Gur G; Bayraktar Y; Ozer D; Ozdogan M; Kayhan B.
Determination of hepatic zinc content in chronic liver disease
due to hepatitis B virus. Hepatogastroenterology (Greece)
Mar-Apr 1998, 45 (20) p472-6.
547. Marchesini G; Bugianesi E; Ronchi M; Flamia R; Thomaseth
K; Pacini G. Zinc supplementation improves glucose disposal in
patients with cirrhosis. Metabolism Jul 1998, 47 (7) p792-8.
548. Reunanen A; Knekt P; Marniemi J; Maki J; Maatela J;
Aromaa A. Serum calcium, magnesium, copper and zinc and risk
of cardiovascular death. Eur J Clin Nutr. Jul 1996, 50 (7)
p431-7.
549. Elmstahl S, Gullberg B, Janzon L, Johnell O, Elmstahl B.
Increased incidence of fractures in middle-aged and elderly
men with low intakes of phosphorus and zinc. Osteoporos Int.
1998;8(4):333-40.
550. Forsleff L, Schauss AG, Bier ID, Stuart S. Evidence of
functional zinc deficiency in Parkinson's disease. J Altern
Complement Med. 1999 Feb;5(1):57-64.
551. Ochi K, Ohashi T, Kinoshita H, Akagi M, Kikuchi H, Mitsui
M, Kaneko T, Kato I. The serum zinc level in patients with
tinnitus and the effect of zinc treatment. Nippon Jibiinkoka
Gakkai Kaiho 1997 Sep;100(9):915-9.
552. Arda HN, Tuncel U, Akdogan O, Ozluoglu LN. The role of
zinc in the treatment of tinnitus. Otol Neurotol. 2003
Jan;24(1):86-9.
553. Di Toro R, Galdo Capotorti G, Gialanella G, Miraglia del
Giudice M, Moro R, Perrone L. Zinc and copper status of
allergic children. Acta Paediatr Scand. 1987 Jul;76(4):612-7.
554. Michaelsson G, Vahlquist A, Juhlin L. Serum zinc and
retinol-binding protein in acne. Br J Dermatol 1977
Mar;96(3):283-6.
555. Michaelsson G, Juhlin L, Vahlquist A. Effects of oral
zinc and vitamin A in acne. Arch Dermatol 1977
Jan;113(1):31-6.
556. Duchateau J, Delepesse G, Vrijens R, Collet H. Beneficial
effects of oral zinc supplementation on the immune response of
old people. Am J Med 1981 May;70(5):1001-4.
557. Mocchegiani E, Muzzioli M, Giacconi R. Zinc and
immunoresistance to infection in aging: new biological tools.
Trends Pharmacol Sci. 2000 Jun;21(6):205-8.
558. Newsome DA, Swartz M, Leone NC, Elston RC, Miller E. Oral
zinc in macular degeneration. Arch Ophthalmol. 1988
Feb;106(2):192-8.
559. Liang JY, Liu YY, Zou J, Franklin RB, Costello LC, Feng
P. Inhibitory effect of zinc on human prostatic carcinoma cell
growth. Prostate. 1999 Aug 1;40(3):200-7.
560. Mossad SB; Macknin ML; Medendorp SV; Mason P. Zinc
gluconate lozenges for treating the common cold. A randomized,
double-blind, placebo-controlled study. Ann Intern Med. Jul 15
1996, 125 (2) p81-8.
561. The world heath report 1998. Life in the 21st century: a
vision for all. Geneva, World Health Organization, 1998.
562. JAMA. Vitamins for Chronic Disease Prevention in Adults.
2002;287:3127-3129.
563. NEJM. Editorial: Eat Right and Take a Multivitamin.
Volume 338:1060-1061; April 9, 1998; Number 15.
564. Public Health Nutr. 2001 Oct;4(5A):1089-97. The efficacy
and safety of nutritional supplement use in a representative
sample of adults in the North/South Ireland Food Consumption
Survey. Kiely M, Flynn A, Harrington KE, Robson PJ, O'Connor
N, Hannon EM, O'Brien MM, Bell S, Strain JJ.
