Transcript HomocysteineJan31 - University of Illinois at Chicago

Homocysteine At The
Crossroads:
Vitamin Status and Disease
Prevention
Dr. Samuel N. Grief, MD, FCFP
University of Illinois at Chicago Family
Medicine
Chair, Panel on Homocysteine and
Screening/Treatment Recommendations
OUTLINE
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Homocysteine and its metabolism.
Homocysteine and nutrition: The vitamin
connection.
Food sources of vitamins Betaine, B12, and
Folate.
Homocysteine and its link to various diseases.
Recommendations regarding homocysteine
screening and treatment.
OBJECTIVES
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Based on scientific evidence, attending physician
will be able to:
1. Define homocysteine
2. Outline homocysteine metabolic pathway
3. List metabolic and vitamin influences on
homocysteine level
4. Identify risk factors for elevated homocysteine
level
5. Determine whether to screen for, and treat,
elevated homocysteine level
Homocysteine has been confirmed
in many independent studies to be a
risk factor for cardiovascular
disease.
References:
Eikelboom JW, Lonn E, et.al. HCY and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med. 1999;131(5):363-375.
Singh H. Selections from current literature: HCY: a modifiable risk factor for cardiovascular disease. Fam Pract 1997;14(4):335-9.
Refsum H, Ueland PM, Nygard O, Vollset SE. HCY and cardiovascular disease. Annu Rev Med. 1998;49:31-62.
Etiology of Cardiovascular
Disease
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Traditional risk factors for coronary artery disease
such as smoking, hypertension, diabetes, and
dyslipidemias can only explain approximately two
thirds of observed clinical events.
Other factors/biochemical markers to consider
include:
CRP
Homocysteine
Other?
Reference: Maxwell SR, Coronary Artery Disease-free radical damage, antioxidant protection and the role of HCY.
Basic Res Cardiol. 2000;95 Supple 1:165-71.
Homocysteine and
Cardiovascular Disease
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Increased incidence and progression of CAD in
patients with diabetes when homocysteine levels
are >11.21 micromol/l was found in a study of
Polish men aged <55 (mean age 49.5 +/- 5.7
years).
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Reference: Skibinska E, Sawicki R, et.al. Kardiol Pol. 2004 Mar;60(3):197-205.
Homocysteine and Endothelial
Effects
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The mechanism by which homocysteine exerts its
cardiovascular disease effects are now being
elucidated. Many authorities have studied this
link. The working hypothesis is that elevated
homocysteine levels:
 1. promote oxidant injury to the vascular
endothelium
 2. impairs endothelium-dependent relaxation
 3. alters the coagulant properties of blood
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References:
Ozdemir R, Barutcu I, et.al. Vascular Endothelial Function and Plasma Homocysteine Levels in Behcet’s Disease, Am J Cardiol
2004;94:522-525.
Austin RC, Lentz SR, Werstuck GH. Role of HyperHCYemia in endothelial dysfunction and atherothrombotic disease. Cell Death Differ.
2004 Jul;11 Supple 1:S56-64.
Homocysteine and Endothelial
Effects
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Other theories include:
a) Elevated homocysteine levels release extracellular
superoxide dismutase from the endothelial wall, causing a
higher likelihood of atherosclerotic changes to the blood
vessels
b) Moderate HyperHCYemia may develop secondary to
cellular immune activation, usually in response to a
chronic disease condition
c) Hyperhomocysteinemia decreases bioavailability of
nitric oxide, thus decreasing endothelial vasodilator
function.
References:
Nihei S, Tasaki H, et.al. HyperHCYemia is associated with human coronary atherosclerosis through the reduction of the ratio of endotheliumbound to basal extracellular superoxide dismutase. Circ J. 2004 Sep;68(9):822-8
Schroecksnadel K, Frick B, Winkler C, et.al. HyperHCYemia and immune activation. Clin Chem Lab Med. 2003;41:1438-1443.
Epidemiology
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Prevalence of hyperhomocysteinemia is not
insignificant:
 1. general population: 5 - 10%
 2. elderly population: 30 - 40%
 3. pts with vascular disease: 20 - 40%.
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References:
Annu Rev Med 1998;49:31-62. HCY and cardiovascular disease. Refsum H, Ueland PM, et.al.
JAMA 1993;270:2693-8. Vitamin status and intake as primary determinants of HCYemia in an elderly population. Selhub J, Jacques PF, et.al.
Jacques PF, Bostom AG, Wilson PW, et.al. Determinants of plasma total HCY concentration in the Framingham Offspring cohort. Am J Clin
Nutr. 2001;73:613-621.
Homocysteine and disease
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Homocysteine elevation is also known to be
strongly associated and linked to several other
medical conditions, including:
osteoporosis
cognitive impairment and decline
increased prenatal complications to women and
unborn children
chronic kidney disease
other conditions
References:
Kidney Int. 2004 Jul;66(1):338-47. Potential cardiovascular risk factors in chronic kidney disease: AGEs, total homocysteine and metabolites,
and the C-reactive protein. Busch M, Franke S, et.al.
Clin Chem. 2004 Aug 19. Screening for Serum Total HCY in Newborn Children. Refsum H, Grindflek AW, Ueland PM, et.al
HOMOCYSTEINE
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Homocysteine, a sulfur containing amino acid, is
formed from methionine, an essential amino acid
found in many animal and plant foods. Methionine
is especially abundant in animal and cereal
proteins.
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Reference: Aleman G, Tovar AR, Torres N. Homocysteine metabolism and risk of cardiovascular disease: Importance of the nutritious status
in folic acid, vitamins B6 and B12. La Revista de Investigacion Clinica. Vol.53, Issue 2, March-April 2001, pp. 141-151.
Homocysteine Metabolism
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Homocysteine is removed either by its
irreversible conversion to cysteine
(transsulfuration) or by remethylation to
methionine.
 There are two separate remethylation
reactions, catalyzed by
betaine:homocysteine methyltransferase and
methionine synthase, respectively.
Homocysteine and Nutrition:
The Vitamin Connection
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The reactions that remove homocysteine are
dependent upon B vitamin status, as both the
transsulfuration enzymes contain pyridoxal
phosphate (B6), while methionine synthase
contains cobalamin (B12), is copper-dependent,
and receives its methyl group from the folic acid
one-carbon pool.
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Reference: Brosnan JT, Jacobs RL, et.al. Methylation demand: a key determinant of homocysteine metabolism. Acta Biochim Pol.
2004;51(2):405-13.
Homocysteine and Nutrition:
The Vitamin Connection
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It is estimated that in about two-thirds of cases of
hyperhomocysteinemia, vitamin deficiency is the
primary cause.
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Reference: Selhub J, Jacques PF, et.al. Vitamin Status and intake as primary determinants of HCYemia in an elderly population. JAMA 1993;
270: 2693-2698.
Fig. 2 - Physiological determinants of total homocysteine
levels
Vitamin B12 and
Homocysteine
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Vitamin B12 is found in foods of animal origin.
 Vitamin B12 status has been studied in different
populations, especially vegetarians.
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Evidence confirms: low vitamin B12 levels
predispose to elevated homocysteine levels.
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References:
Waldmann A, Koschizke JW, et.al. HCY and cobalamin status in German vegans. Public Health Nutr. 2004 May;7(3):467-72.
Flood VM, Webb KL, Smith W, et.al. Prevalence of low serum folate, red cell folate, serum vitamin B12 and elevated HCY. Asia Pac J Clin
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Nutr. 2004;13(Suppl):S85.
FOOD
Food sources of Vitamin B12
BEST FOOD SOURCES OF VITAMIN B12
PORTION SIZE
AMOUNT (MCG)
Liver
100 grams
70.58
Seafood
100 grams
6.88
Salmon
100 grams
2.80
Beef Hamburger
100 grams
2.50
Eggs
100 grams
1.11
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MCG: Micrograms
NB: 100 grams=3.5 ounces
FOLATE
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Folate, aka folic acid, found in numerous foods, is
a water-soluble B-vitamin and enzymatic cosubstrate for the synthesis of methionine from
homocysteine.
 Folic acid deficiency is the most common cause
of elevated HCY levels.
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Reference: Jacques PF, Selhub J, et.al The effect of folic acid fortification on plasma folate and total HCY concentration. N Engl J Med
1999;13:1449-1454.
Folate
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The U.S. Food and Drug Administration’s
implementation of mandatory fortification of
grains and cereals with folic acid on January 1,
1998 is a direct result of research studies
confirming folate’s HCY-lowering effects, as well
as studies linking low folate levels with an
increased incidence of neural tube defects.
References:
Tucker KL, Selhub K, et.al. Dietary intake pattern related to plasma folate and HCY concentrations in the Framingham Heart Study. J Nutr
1996;126:3025-3031.
Food and Drug Administration. Food Standards: amendment of standards of identity for enriched grain products to require addition of folic
acid. Federal Register. 1996;61(44):8781-97.
Riddell, LJ, Chisholm A, et.al. Dietary strategies for lowering HCY concentrations. Am J Clin Nutr. 2000; 71(6): 1448-54.
Vitamins and Food sources
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Folic acid - Green leafy vegetables (e.g. spinach,
broccoli), legumes (e.g. lentils, chick peas, lima
beans), orange
 Vitamin B6 - Meat, poultry, fish, green leafy
vegetables, legumes, seeds, potatoes, cantaloupe,
milk, egg yolks, cereals, grains, wheat, wheat
germ
 Vitamin B12 - Beef, poultry, fish (particularly
crab, oyster, salmon and herring), liver, kidney,
soy, fruit juice, dairy products, egg yolks, fortified
cereals, breads
Homocysteine and Nutrition:
The Vitamin Connection
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Betaine, a choline derivative, is important because
of its role in methyl group donation to
homocysteine to form methionine.
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Reference: Zeisel SH, Mar MH, et.al. Concentrations of choline-containing compounds and betaine in common foods. J Nutr. 2003
May;133(5): 1302-7.
Many foods are rich in Betaine
Studies confirm betaine’s ability to reduce homocysteine levels
in the face of excess methionine intake.
References:
Steenge GR, Verhoef P, Katan MB. Betaine supplementation lowers plasma HCY in healthy men and women. J Nutr. 2003 May;133(5):1291-5.
Olthof MR, van Vliet, et.al. Low dose betaine supplementation leads to immediate and long term lowering of plasma HCY in healthy men and women. J
Nutr. 2003 Dec;133(12):4135-8.
Food sources of Betaine
Choline and Betaine Food Sources
Amount (mg/100g food)
Wheat Bran
Wheat Germ
Spinach
Beef Liver
1339
1293
645
418
Chicken Liver
Eggs
Pretzels
Shrimp
Wheat Bread
Bacon
Dried Soybeans
Pork
290
251
237
218
201
125
116
103
VISP STUDY
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In the recently completed Vitamin Intervention
for Stroke Prevention (VISP) study, Toole, et.al.
investigated the homocysteine-lowering effects of
B vitamins in over 40,000 men with established
history of cerebrovascular accidents.
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Reference: Toole JF, Malinow MR, Chambless LE, et.al. Lowering HCY in pts. With ischemic stroke to prevent recurrent stroke, MI, and
death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004;291:565-575.
VISP STUDY
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The VISP randomized controlled trial was
undertaken to assess whether reducing HCY
levels by vitamin supplementation would reduce
risk of recurrent strokes, CHD, and death.
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Reference: Toole JF, Malinow MR, Chambless LE, et.al. Lowering HCY in pts. With ischemic stroke to prevent recurrent stroke, MI, and
death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004;291:565-575.
VISP STUDY
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High-dose vitamin supplementation
participants received:
25mg of pyridoxine
400mcg of cobalamin
2.5mg of folic acid
low-dose was 200mcg, 6mcg, and 20mcg,
respectively.
Reference: Toole JF, Malinow MR, Chambless LE, et.al. Lowering HCY in pts. With ischemic stroke to prevent recurrent stroke, MI, and
death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004;291:565-575.
RDA for Vitamins B6, B12 and
Folate
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Vitamin B6
 Vitamin B12
 Folate
2 mg
6 mcg
400 mcg
VISP STUDY
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Even though a mean reduction of HCY in the
high-dose vitamin supplementation group of 2
micromol/l greater than in the low-dose group
was achieved, no significant effect on the above
end points occurred.
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Reference: Toole JF, Malinow MR, Chambless LE, et.al. Lowering HCY in pts. With ischemic stroke to prevent recurrent stroke, MI, and
death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004;291:565-575.
VISP STUDY
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The results did not confirm a reduction in
recurrent strokes in study patients, however, the
homocysteine-lowering effects of folic acid,
vitamin B6 and vitamin B12 were confirmed.
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Reference: Toole JF, Malinow MR, Chambless LE, et.al. Lowering HCY in pts. With ischemic stroke to prevent recurrent stroke, MI, and
death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004;291:565-575.
SCREENING AND TREATMENT RECOMMENDATIONS FOR
HOMOCYSTEINE
In 2000, the Canadian Task Force on Preventive Health Care concluded
that there was a link between total HCY levels and CAD based on cohort
and case-control studies, but found the evidence insufficient to
recommend for or against HCY screening in both the general and highrisk populations.
Reference: CMAJ.2000 Jul 11;163(1):21-9. Preventive health care, 2000 update: screening and management of hyperHCCYemia for the prevention of CAD evens. The
Canadian Task Force on Preventive Health Care. Booth GL, Wang EE.
SCREENING AND TREATMENT RECOMMENDATIONS FOR
HOMOCYSTEINE
An expert panel led by Refsum reviewed multiple,
well-designed, randomized controlled trials and
concluded the following:
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A) Vitamin “B” intake directly impacts the level of homocysteine
B) Folate deficiency is a strong determinant on homocysteine levels
C) Coffee consumption may very well increase total homocysteine
levels
D) Unhealthy lifestyle and poor diet is a cause of moderately high
levels of homocysteine (15-30 micromol/l).
Reference: Refsum H, Smith DA, et.al. Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion. Clin
Chem 2004; 50: 3-32.
HOMOCYSTEINE IS AT THE CROSSROADS OF
VITAMIN STATUS (B6, B12, FOLATE)
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Screening for HCY may indirectly assess a
patient’s vitamin B6, B12 and folate status, thus
offering a useful window into the patient’s
nutrition profile.
 Total homocysteine measurements are now
recommended to screen for vitamin deficiency in
both the general and high risk populations.
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Reference: Clarke R, Refsum H, et.al. Screening for vitamin B12 and folate deficiency in older persons. Am J Clin Nutr 2003; 77: 1241-7.
Screening Recommendations
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HCY evaluation is now recommended for the
following high risk populations:
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age 65 years and over with or without co-morbid conditions
in patients with any of the following medical conditions, including:
diabetes
smoking history
established cardiovascular disease or multiple cardiovascular risk
factors
renal disease
nutritional deficiencies
cognitive disorders
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References:
Nygard O, Nordrehaug JE, Refsum H, et.al. Plasma HCY levels and mortality in patients with CAD. N Engl J Med. 1997;337:230-236.
Fallest-Strobl PC, Koch DD, et.al. HCY: A New Risk Factor for Atherosclerosis. American Family Physician. Oct.15, 1997. Vol.56, No.6.
Malinow MR, Bostom AG, Krauss RM. HCY, diet, and cardiovascular diseases: a statement for health care professionals from the Nutrition
Committee, American Heart Association. Circulation 1999;99:178-182.
Nilsson M. Cobalamin and folate deficiency. Paradigm shift in screening. Rondel 2004;18. http://www.rondellen.net.
Therapeutic Goals
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Target plasma HCY levels of <10 micromol/l
are now being recommended by various
medical authorities.
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References:
Stanger O, Herrmann W, et.al. Clinical use and rational management of HCY, folic acid, and B vitamins in cardiovascular and thrombotic
disease. Z Kardiol.2004 Jun; 93(6):439-53.
Malinow MR, Bostom AG, et.al. Homocysteine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition
Committee, American Heart Association. Circulation 1999; 99: 178-82.
Ubbink JB. What is a desirable homocysteine level? In: Carmel R, Jacobsen DW, eds. Homocysteine in health and disease. Cambridge, UK:
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Cambridge University Press, 2001: 485-90.
Some experts suggest that target homocysteine levels should be realistically below values where
risk for cardiovascular disease substantially increases.
Reference:Booth, G. CMAJ. 2000 July; 163(1): 21-29.
TABLE 3: Homocysteine level relation to overall mortality and CAD-related death.
High Risk Population a
Yes
Screen for HCY
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Level > 10 micromol/l
Treatment
Do not screen for HCY
Level < 10 micromol/l
Continue monitoring/treating other medical conditions
No treatment
Vitamins B6, B12, Folate
aHigh
No
May recommend MVI
risk population defined in “Recommendations regarding HCY screening” section.
Why Rx Vitamins?
 Appropriate
vitamin awareness,
knowledge of Rxing vitamins, and
ability to recommend nutritional
sources of vitamins will become more
critical for physicians to master as the
future of medicine changes from a
diagnostic/therapeutic mode to a more
preventive/holistic style.
RDA for Vitamins B6, B12 and
Folate
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Vitamin B6
 Vitamin B12
 Folate
2 mg
6 mcg
400 mcg
Treatment Recommendations
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Add to the overall treatment plan of your
high-risk patient a B-complex vitamin
containing, at a minimum, the following Bvitamins:
 Folic acid
1.0 mg
 Vitamin B6
10mg
 Vitamin B12 1.0mg
Cost of Recommendations*
Folic Acid
 Vitamin B6
 Vitamin B12
1.0 mg
10mg
1.0 mg
3 cents
2 cents
6 cents
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TOTAL COST:
11 cents/day
11 cents x 30 days = $3.30/month
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1 Tall Caffe Latte (Starbucks)
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*Cost taken from AWP at UIC Hospital
: $3.30 (plus tax!)
Future Recommendations
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Future research should include various
vitamin preparations and their ability to
lower specific endpoints, i.e. CVD, cancer,
kidney disease, etc.
TOP FIVE HEALTH
RESOLUTIONS
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5. Stop Smoking
 4. Exercise More
 3. Lose Weight
 2. Become a Better Person
And the #1 Health Resolution is…
 1. Eat Healthier
10 Essentials for
Healthy Living
In order to achieve a quality of life that permits both physical and psychological
wellness, it is important to do positive acts that promote both your well being and those
around you. Reflect on these 10 essentials for healthy living as you move along your
life’s journey.
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1. Breathe Deeply
Air is the cornerstone of life. Every moment of every day your body exchanges carbon dioxide for oxygen to keep
each cell in your body alive and functioning. A rich supply of oxygen can make the difference between feeling tired
and stressed and youthful and focused. Take at least five deep breaths from your abdomen several times per day.
2. Drink Water
Water is essential for everything your body does. In fact, you are mostly water! Nutrient absorption, blood flow,
respiration, elimination and your ability to see and hear require adequate consumption of pure, clean water. Your body
cannot effectively store the water you need throughout the day. Drink water often.
3. Sleep Peacefully
Sleep is the only time your body has to repair and rejuvenate every organ and system in your body. Sleep deprivation
causes cellular damage, and limits the production of enzymes and hormones your body needs to keep your cells
healthy, and prevent premature aging. Sleep also has a powerful impact on your emotional health - it eases stress and
helps you cope with the ups and downs of your day.
4. Eat Nutritiously
Food has a powerful impact on your body. Every day, food, in large part, determines how you feel and how your body
functions. A balanced diet, rich in whole foods, combined with quality nutritional supplements created to meet your
specific needs, will give you the energy you need today, and the disease-fighting strength you need to build a healthy
future.
Reference: www.trivita.com
10 Essentials for
Healthy Living
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5. Enjoy Activity
Your body was created to move - and move often. Activity increases your circulation, speeding
oxygen, nutrients and water to your cells. Your lymphatic system requires activity to purge your body
of deadly toxins. Activity also triggers your brain to release health-giving hormones and enzymes,
which lift your spirit while they bolster your immune system. A small investment in daily moderate
activity will enable you to reap tremendous health benefits.
6. Give and Receive Love
As you give and receive love freely and generously, you will be blessed with meaningful, lifelong
relationships and cherished memories that will bring joy in happy times, and strength and peace in
difficult times.
7. Be Forgiving
It sounds so simple, and yet can be so difficult. Extending and asking for forgiveness is one of the
four principles of emotional health because it is a key to your ability to give and receive love. In its
purest form, forgiveness is not an act, but an attitude. As you cultivate the ability to live in a state of
forgiveness, your anger, frustration and guilt are replaced with peace, love and acceptance.
Reference: www.trivita.com
10 Essentials for
Healthy Living
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8. Practice Gratitude
Sincere gratitude will lift and inspire you. Recognizing and appreciating all you have empowers you
to find and express true joy.
9. Develop Acceptance
When you develop the ability to identify and accept the circumstances in your life you cannot
change, yet strive to make positive changes whenever and wherever you can, you will discover
lasting peace and hope.
10. Develop a Relationship with God
You develop a relationship with God the same way you build a relationship with those around you through sharing and listening. By offering a simple prayer daily, you will enjoy a sense of well being
you will not experience in any other way.
Reference: www.trivita.com
REFERENCES
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Homocysteine and nutrition: The vitamin connection
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1.
Aleman G, Tovar AR, Torres N. Homocysteine metabolism and risk of cardiovascular disease: Importance of the nutritious status in folic acid, vitamins B6 and B12. La
Revista de Investigacion Clinica. Vol.53, Issue 2, March-April 2001, pp. 141-151.
2.
Brosnan JT, Jacobs RL, et.al. Methylation demand: a key determinant of homocysteine metabolism. Acta Biochim Pol. 2004;51(2):405-13.
3.
Selhub J, Jacques PF, et.al. Vitamin Status and intake as primary determinants of HCYemia in an elderly population. JAMA 1993; 270: 2693-2698.
4.
Boushey CJ, Beresford SA, et.al. A quantitative assessment of plasma HCY as a risk factor for vascular disease. Probably benefits of increasing folic acid intakes. JAMA
1995;274:1049-57.
5.
Rasmussen K, Moller J, et.al. Age- and gender-specific reference intervals for total HCY and methylmalonic acid in plasma before and after vitamin supplementation. Clin
Chem 1996;42:630-6.
6.
Wald DS, Bishop L, Wald NJ, et.al. Randomized trial of folic acid supplementation and serum HCY levels. Arch Intern Med. 2001;161:695-700.
7.
Toole JF, Malinow MR, Chambless LE, et.al. Lowering HCY in pts. With ischemic stroke to prevent recurrent stroke, MI, and death: the Vitamin Intervention for Stroke
Prevention (VISP) randomized controlled trial. JAMA 2004;291:565-575.
8.
Schnyder G, Roffi M, Pin R, et.al. Decreased rate of coronary restenosis after lowering of plasma HCY levels. N Engl J Med. 2001;345:1593-1600.
9.
Marcucci R, Zanazzi M, Bertoni E, et.al. Vitamin supplementation reduced the progression of atherosclerosis in hyperHYCemic renal-transplant recipients.
Transplantation. 2003;75:1551-1555.
10. Jacques PF, Selhub J, et.al The effect of folic acid fortification on plasma folate and total HCY concentration. N Engl J Med 1999;13:1449-1454.
11. Tucker KL, Selhub K, et.al. Dietary intake pattern related to plasma folate and HCY concentrations in the Framingham Heart Study. J Nutr 1996;126:3025-3031.
12.
Food and Drug Administration. Food Standards: amendment of standards of identity for enriched grain products to require addition of folic acid. Federal Register.
1996;61(44):8781-97.
13. Waldmann A, Koschizke JW, et.al. HCY and cobalamin status in German vegans. Public Health Nutr. 2004 May;7(3):467-72.
14. Flood VM, Webb KL, Smith W, et.al. Prevalence of low serum folate, red cell folate, serum vitamin B12 and elevated HCY. Asia Pac J Clin Nutr. 2004;13(Suppl):S85.
15.
Strassburg A, Krems C, Luhrmann PM, et.al. Effect of age on plasma HCY concentrations in young and elderly subjects considering serum vitamin concentrations and
different lifestyle factors. Int J Vitam Nutr Res. 2004 Mar;74(2): 129-36.
16. Zeisel SH, Mar MH, et.al. Concentrations of choline-containing compounds and betaine in common foods. J Nutr. 2003 May;133(5): 1302-7.
17. Steenge GR, Verhoef P, Katan MB. Betaine supplementation lowers plasma HCY in healthy men and women. J Nutr. 2003 May;133(5):1291-5.
18.
Olthof MR, van Vliet, et.al. Low dose betaine supplementation leads to immediate and long term lowering of plasma HCY in healthy men and women. J Nutr. 2003
Dec;133(12):4135-8.
19. McGregor DO, Dellow WJ, et.al. Betaine supplementation decreases post-methionine HyperHCYemia in chronic renal failure. Kidney Int. 2002 Mar;61(3):1040-6.
20. Riddell, LJ, Chisholm A, et.al. Dietary strategies for lowering HCY concentrations. Am J Clin Nutr. 2000; 71(6): 1448-54.
21. Clarke R, Refsum H, et.al. Screening for vitamin B12 and folate deficiency in older persons. Am J Clin Nutr 2003; 77: 1241-7.
REFERENCES
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Homocysteine and nutrition: Part B
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1.
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Case Presentations and discussions
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Homocysteine and endothelial effects
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Homocysteine and Genetics
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REFERENCES
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Recommendations regarding homocysteine screening
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2.
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REFERENCES
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Executive Summary Recommendations
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QUESTIONS?
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THANK YOU!
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HAVE A GREAT DAY!