GSE
Too Much Meat & Dairy / NOT Enou
Too much meat & dairy / NOT enough B-vitamins causes inflammation
==> Elevated protein-corrosive homocysteine (HC)
HC damages proteins - E.g. Collagen
and elastin in connective tissue;
The amino acid homocysteine is formed from the
metabolism of the essential amino acid, methionine, abundant in red meat and
dairy products. HC is not
directl y obtained from the diet; Vegetables, with few exceptions (E.g,
sesame seeds and Brazil nuts), are low in methionine;
Adequate amounts of
folic acid (B9) and other B vitamins
are needed to convert homocysteine into less toxic
amino-acids - Vitamin
B2 (riboflavin) and magnesium are also involved in homocysteine metabolism.
The two main possible pathways for HC are:
- Remethylation (~50%) - utilizes
active folate (MTHR), B12 and the enzyme MTHFR to convert
homocysteine back to methionine. (Also this conversion occurs in kidney and
liver via betaine homocysteine methyltransferase (BHMT) which transfers a methyl
group to homocysteine via the demethylation of trimethylglycine (TMG /aka
betaine, which serves as a methyl donor) to dimethylglycine (DMG)) ;
- Transsulfuration (~50%) -
utilizes the
active form of vitamin B6 (pyridoxal-5'-phosphate) and the enzyme
cystathionine-synthase (CBS). Once formed from cystathionine, cysteine can then
be used by the body to make protein and
glutathione
(GSH), a powerful antioxidant.
If either of these pathways are
impaired (E.g. due to a deficiency of B6, B12, folate , betaine), then plasma
fasting HC concentrations are increased, significantly so in the remethylation
pathway.
Low
thyroid activity increases HC
-
Low thyroid activity depletes intracellular
magnesium promoting HC accumulation
McCully. K.S. (1983),
"Homocysteine theory: Development and current status. Atherosclerosis Reviews
11: 157-246.
- Fluoride, Chlorine, and bromine lower thyroid
activity and thus increase HC -
Iodine
supplementation counters these goitrogens;
Yiamouiannis, J.
(1986), Fluoride: The Aging Factor, Delaware, Ohio: Health Action Press.
McCully. K.S. (1983), "Homocysteine theory: Development and current status.
Atherosclerosis Reviews 11: 157-246.
Typical Levels. Common levels in Western populations are 10 - 12 μmol/L and levels of 20
μmol/L
are found in populations with low B-vitamin intakes or in the older elderly.
Studies indicate that those with HC values >or = 6.3 μmol/L are at increased risk of
atherosclerosis
Homocysteine
Studies Collaboration. Homocysteine and risk of ischemic heart disease and
stroke: a meta-analysis.
JAMA . 2002;288:2015-2022,heart attack and strokeBroxmeyer L. Heart disease: the greatest 'risk' factor of them all.
Med Hypotheses . 2004;62:773-779.
Women have 10-15% less HC during their reproductive decades than men which may
help explain the fact they suffer heart attacks on average 10 to 15 years later
than men; A practical HC goal after age 50 is < 7-8 μmol/L;
Higher HC levels are
associated with: cancer, diabetes,
CVD, age-related macular degeneration, hearing loss, brain atrophy, dementia,
migraine and thyroid disease, prescription drug use, age, declining ability to
absorb B12, deteriorating kidney function, smoking, coffee consumption, and excessive alcohol
intake, lack of exercise, obesity, stress, and inheriting a variant gene for
MTHFR;
High HC level in blood is a strong risk factor for CVD
Credit for graph on right: G Alfthan et al, Plasma homocysteine and cardiovascular disease mortality.
Lancet 1997
HC is a 'corrosive' of the three main structural
components of the artery - theconnective tissue proteins collagen, elastin and proteoglycans
(e.g. fibrillin is a glycoprotein needed to form elastic fibers). HC prevents
the formation of stable peptide bonds by tending to cleave to itself.
Elevated homocysteine also occurs in the rare
hereditary disease homocystinuria. Also in those people with a
more common genetic trait, which decreases activity of an enzyme called MTHFR
(see inset), which metabolizes folic acid to its active form; however, a
significant reduction in plasma HC is achieved by taking an active folate
(5-MTHF) supplement.
MTHFR
An enzyme used to produce a substrate involved in the beneficial
conversion of HC to methionine. A DNA sequence variant (polymorphism) in MTHFR results in its
decreased enzymatic activity. This trait is present in about 10% of the
world population and it is linked to an increased incidence of
thrombosis and CVD, occurring more often in people with above minimal
levels of HC (~6 μmol/L).
Cholesterol is oxidized
by HC to generate oxysterols (oxygenated derivatives
of cholesterol) and arterial damage is
proportional to the concentration of oxysterols
Gey KF et
al, Plasma levels of antioxidant vitamins in relation to ischemic disease and
cancer. Am J Clin Nutr 1987;45:1368-1377;
(LDL cholesterol is only an accomplice to arterial damage through oxidative
modification). HC also generates oxysterols in
food exposed to high heat and oxygen E.g powdered egg yolk/milk, gelatin (HC is
the only dietary substance to do so, other than damaged fatty acids,such as trans fatty acids).Processed foods may increase oxysterol presence 1000 times higher than normal.
Evidence of HC
involvement in CVD includes:
-
Even slightly elevated HC level promotes tiny
clots that initiate arterial damage and large clots that precipitate heart
attacks and stroke s
Gibson JR et al, Pathological Findings in homocystinuria, J Clin Pathol 1964;
Morin RJ et al, The Role of cholesterol oxidation products in the pathogenesis
of atherosclerosis, Ann Clin & Lab Sci., 1991; Editorial: Is vitamin B6 an
antithrombic agent? Lancet 1981
- Baboons infused with HC
for 5-30 days developed arterial damage proportion to HC concentration - There was no
correlation to cholesterol.
Harker LA
et al, Homocysteinemia: Vascular injury and arterial thrombosis, New Eng Journ
Med, 1974.
-
Men with high HC levels had > 3 times more heart attacks than those with low HC
levels
-
Men with 3 clogged coronary arteries had higher
HC than men with 1
Malinow MR. Risk fro
arterial occlusive disease. In hyperhomocysteinemia an innocent bystander? Can.
J Cardiol 1989; Stampfer M et al, A prospective study of plasma homocysteine and
risk of myocardial infarction in US physicians. JAMA 1992
-
Anti-atherogenic, anti-clotting benefit of fish
oil may result from lowering HC
Olszewski AJ et al, Fish oil decreases serum homocysteine in hyperlipemic men,
Coronary Artery Dis 1993
During pregnancy high
estrogen
levels promote HC metabolismand
deter lipid peroxidation -
protecting
pregnant mothers from CVD
Ueland , P.M. & H. Refsum (1989). "Plasma homocysteine, a
risk factor for vascular disease: Plasma levels in health, disease and drug
therapy,"Jour. Lab. Clin. Med. 114: 473-501.
Yaki , K. & S. Komura (1986), "Inhibitory effect of female
hormones on lipid peroxidation,"Biochem. Int. 13: 1051-1055.
HC weakens the immune system
Impedes the action of macrophages
McCully . K.S. (1983), "Homocysteine theory: Development
and current status. Atherosclerosis Reviews 11: 157-246.
Vitamin B6 mediates homocysteine connection to heart health
Long-term B6
supplementation protects against heart problems - i n 1950, Dr. Moses M. Suzman
(neurologist/internist) in S. Africa started his patients on a daily dose of 100
mg B6, before they were diagnosed with heart problems. Over the course of
44 years, Dr. Suzman could not point to a single one of his tens of thousands of
patients who had had a coronary spasm, cardiac arrest or stroke, and "far fewer
cardiac problems than would have been expected."In 1969, he changed the daily dose to 200 mg B6 (half as a complex) and
600 IU vitamin E . In 1972, he also added
vitamin C, selenium ,
magnesium and
other nutrients;
B6 deficiency:
• Common in pregnancy
• Many peoples' livers can not
convert B6
supplement pyridoxine hydrochloride to pyridoxal phosphate (PLP) - the active form of
B6 in the body.
• Consequence of methionine-rich high-animal protein
diets and high dietary sugar;
Vitamin B6
seems to protect against oxysterols -
B6
has been found to act as an antioxidant in high enough concentration by
several researchers protecting against oxysterols