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Folate plays an important role in the formation of red blood cells. Specically, folate, along with B12

the formation of hemoglobin in red blood cells. Several studies have addressed the relationship between Alzheimer Disease and low serum concentrations of folate, vitamin B12

been linked to a build-up of homocysteine in the blood, increasing the risk of heart attacks, strokes and other cardiovascular diseases.

, and vitamin B6.23 Studies have indicated the need for Vitamins B6

turn, acts directly to convert cystathionine to cysteine.25 This process, which is reversible, requires both vitamins B12

It, in

involved in this process, as it functions as a cofactor for the enzyme Cystathionine -synthase (CBS), the rst, and rate-limiting enzyme in the transsulfuration pathway, which is required to convert Hcy to cystathioine.24

and folic acid as cofactors. Moreover, Vitamin B12 is a required cofactor for methionine synthase, while,

folic acid in the management of cardiovascular related problems, as they play a major role in homocysteine (Hcy) metabolism and concentration regulation. The metabolism of homocysteine occurs via two major pathways, the rst and most predominant of these is the remethylation of Hcy to methionine. Vitamin B6

, B12 is also and Furthermore, low folate levels have , is essential for

its role as a methyl donor, TMG also participates in the manufacture of carnitine, and serves to protect the kidneys from damage.

Choline Bitartrate is involved in many physiological processes, including normal metabolism and transport of lipids, methylation reactions, neurotransmitter synthesis, and, like TMG, it functions as a methyl donor.

decient diet under controlled conditions, it was found that 77% of men, 80% of postmenopausal women, and 44% of premenopausal women developed fatty liver, liver damage, and/or muscle damage.32

As a consequence of lower estrogen concen- trations in these women, in conjunction with a low- choline diet, an increased susceptibility for the risk of organ dysfunction is plausible.

be a judicious decision to support the aging population. L-Methionine (C5

, B12 and folate,26

amino acid, and a primary component of homocysteine metabolism. It is a required component for growth and tissue repair, and also aids in improving the tone and pliability of skin, hair, and nail strength. Additionally, it is involved in many detoxifying processes. The sulphur component of the molecule functions to provide cellular protection from pollutants, slows cellular aging, and is essential for absorption and bio-availability of the minerals selenium and zinc.27

H11 NO2

Methionine also participates in the chelation of heavy metals, including lead and mercury.29

metabolism due to chronic alcohol consumption have been correlated with the pathogenesis of alcoholic liver disease.28

the process of methyl donation either directly via the methylation of homocysteine, or indirectly by supporting the body’s production of SAM-e.

Trimethylglycine (TMG) also known as betaine is typically derived from beet root. Consequently, the terms trimethylglycine and betaine are used interchangeably. Structurally, TMG consists of the amino acid glycine with three methyl groups attached to it. It is classied as a cholinergic compound - a compound dened as one that results in an increased level of acetylcholine in the brain following consumption.30

TMG plays a role in supporting

Along with folate, TMG serves a vital role in methylation processes in the body, and participates functionally as a methyl donor. The donation of methyl groups by TMG is very important for proper liver function, cellular replication, and detoxication reactions. In addition to

92 Alterations in hepatic methionine

as noted previously, folic acid is a required cofactor for 5, 10-methylenetetrahydrofolate reductase. Finally, according to Rakel D, altered methylation reactions occur with age primarily as a result of deciencies in vitamins B6

S) is a sulfur containing essential thus supplementation may

menopausal women have a higher dietary requirement for choline than do premenopausal women. One study also noted that the bacterial taxa predicted the degree of subject susceptibility to fatty liver when dietary choline is decient.35

Choline bitartrate is a stable form of choline.

Collectively, the combination of SAM-e and the other nutrients discussed above provides support for numerous health circumstances, and may also aide to improve intellectual performance. The use of SAM-e has also been associated with a deceleration of the aging process, and may be benecial for attention decit-hyperactivity disorder (ADHD), multiple sclerosis, spinal cord injury, seizures, migraine headache, and other conditions, as noted above. The additional components discussed function to provide collective support for methylation and homocysteine metabolism.


Antidepressant drugs (Fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), amitriptyline (Elavil), clomipramine (Anafranil), imipramine (Tofranil), and others) interact with SAM-e. o Depression medications may increase serotonin levels, resulting in side effects, such as heart problems, shivering, and anxiety.

Those with Parkinson’s disease should avoid the use of SAM-e.

2. Chiang PK, Gordon RK, Tal J, et al. S-Adenosylmethionine and methylation. FASEB J. 1996 10:471–80.

3. food,-herbs-supplements/professional.aspx? productid 786.

THE ORIGINAL INTERNIST JUNE 2016 (Continued on next page)

o Medications for depression (MAOIs) interacts with SAM-e. Medications used for depression include phenelzine (Nardil), tranylcypromine (Parnate), and others.

References 1. Cheng , Blumenthal RM. S-Adenosylmethionine-dependent methyltransferases: structures and functions. World Scientic Publication Co, 1999.

Because of this, post-

Estrogen stimulates the endogenous synthesis of phosphatidylcholine via the phosphatidylethanolamine N-methyltransferase (PEMT) pathway, thus it is the likely explanation for the high percentage of choline deciency in response to a low-choline diet in post-menopausal women.33,34

In healthy adults fed choline-

deciency in choline results in impaired VLDL secretion and accumulation of fat in the liver (steatosis), which may result in liver damage.31


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