Vitamin C’s relationship with cancer risk appears complex and context-dependent. While maintaining adequate blood levels (≥60.19 μmol/L) is associated with reduced cancer mortality, supplementation may increase postmenopausal breast cancer risk by 32% in women with already high dietary intake. This suggests a U-shaped relationship where both deficiency and excess may be detrimental, emphasizing the importance of personalized approaches to vitamin C intake.
Vitamin B6 is an antioxidant and coenzyme involved in amino acid, carbohydrate and lipid metabolism. Humans cannot directly produce active vitamin B6 (pyrixodal phosphate). However, salvage pathways allow the enzymatic conversion of vitamin B6 vitamers, including pyridoxine, pyridoxal and pyridoxamine by the enzyme pyridoxal kinase, into active vitamin B6.
In the body, active vitamin B6 is involved in metabolic reactions including GABA synthesis, monoamine neurotransmitter metabolism, the metabolism of polyunsaturated fatty acids and phospholipids, amino acid metabolism and the conversion of tryptophan to niacin.
Vitamin B6 reduces homocysteine levels by acting as a coenzyme for both cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) in the transsulfuration pathway following a postprandial methionine-load (after a meal). In the fasting state, homocysteine is primarily metabolised via the remethylation pathway which does not require vitamin B6.
In the transsulfuration pathway, homocysteine is converted to cystathionine by CBS, then to cysteine by CSE. During moderate vitamin B6 deficiency, CSE exhibits much greater loss of activity compared to CBS. However cysteine production is preserved due to an accumulation of cellular and plasma cystathionine in a larger substrate pool which compensates for reduced CSE activity. As CBS is a vitamin B6-dependent enzyme, CBS deficiency (typically genetic causes) can result in elevated fasting and post-methionine load homocysteine due to impaired synthesis of cystathionine from homocysteine. Elevated homocysteine levels increase oxidative stress, may inhibit nitric oxide synthesis, increase vascular endothelial cell damage and accelerate low-density lipoprotein (LDL) deposition in arteries.
Vitamin B6 may significantly decrease the rate of formation of kidney stones in patients with type I primary hyperoxaluria, a condition caused by a deficiency of the liver-specific enzyme alanine-glyoxylate:aminotransferase by reducing levels of urinary oxalate. The protective effect of vitamin B6 supplementation for kidney stones appears to only occur in women (-34% risk) and not men.
Even though it is water soluble, yes it can accumulate, especially at the higher doses found in supplements. The primary way this happens is via unaware supplementation. Usually people are unaware that their product contains b6 - it's in a lot of products that are not advertised to contain it.
So even though it is water soluble it can still accumulate when taken at these high doses. Most supplements contain pyridoxine, which can acumulate and damage peripheral nerves. Indeed the form of B6 is important, and manufacturers take advantage of the fact that consumers (and medical practitioners) are unaware of the difference. Taking P-5-P may be less risky than pyridoxine hydrochloride, a cheaper option that is included in most supplements.
Serious side effects from long term high dose vitamin B6 include peripheral neuropathy. Doses exceeding 500 to 1000 mg per day pose the greatest risk but prolonged intake of lower doses may also result in this side effect. The Therapeutic Goods Association of Australia has found that peripheral neuropathy can occur at doses of less than 50 mg.
In pregnant adult women, vitamin B6 is likely safe at a dose of up to 100 mg per day. In adolescent pregnancy, vitamin B6 is likely safe at a dose of up to 80 mg per day.
In lactating adult women, vitamin B6 is likely safe at a dose of up to 100 mg per day. In adolescents who are lactating, vitamin B6 is likely safe at a dose of up to 80 mg per day.
In children, vitamin B6 is likely safe at a daily dose of 30 mg (1-3 yrs), 40 mg (4-8 yrs), 60 mg (9-13 yrs) and 80 mg (14-18 yrs).
The likelihood of side effects increases at doses higher than 200 mg per day.
In 2023, the European Food Safety Authority set an upper limit of vitamin B6 of 12 mg per day for adults, and 2.2 to 10.7 mg per day for infants and children.
See: https://inspectsupplement.com/vitamin-c/#Cancer
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