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 directly 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 - the connective 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.

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 strokes

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 - in 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