Research is now delving deeper into a number of health related illnesses that could be directly or indirectly linked to a Vitamin B12 deficiency. Some of these illnesses are age related macular degeneration, neural tube defects, cardiovascular disease, cognitive decline, osteoporosis and other age related declines.
Age related macular degeneration (AMD):
Vitamin B12 deficiency has been associated with the development of age related macular degeneration (AMD) and risk of frailty, both leading causes of disability in the elderly.
AMD is the leading cause of vision loss in the elderly. Risk factors include increasing age, family history, hypertension, smoking, obesity, sunlight exposure and hypercholesterolemia. Some but not all cross sectional studies have found lower vitamin B12 concentrations in AMD cases. However, a recent RCT with 5205 female health professionals at risk of vascular disease found a 34% reduction in the relative risk of AMD after supplementation with vitamins B12, B6 and folate (daily doses of 1 mg, 50 mg, 2.5 mg respectively).
Frailty in the elderly:
Frailty is characterised by muscle wasting, diminished strength, often with weight loss with or without reduced nutritional intake. Frailty is associated with an increased vulnerability to stresses, causing longer and more complicated recovery from illness or surgery.
Increased risk of frailty and disability has been associated with poor B vitamin status. Subjects with vitamins B12 and B6 in the lowest quintiles and subjects with elevated MMA and tHcy concentrations, have been found to have increased risk of decline in physical function and the development of frailty. Two cross sectional studies found the length of hospital stay was associated with poor vitamin B12 status as assessed by MMA and serum vitamin B12 concentrations. To date there are limited studies, however, if improvements in nutrition can delay frailty progression, it could significantly enhance the independence of the increasing numbers of older people.
Neural tube defects (NTD):
Low vitamin B12 status has been postulated as a potential risk factor for neural tube defects (NTD) since vitamin B12 acts as a cofactor for methionine synthase in the folate cycle. When vitamin B12 supply is low, the folate needed for DNA synthesis remains trapped in the methylation cycle and cell replication is impaired. The studies consistently report a 2-4 fold increased risk of NTD with low vitamin B12 status. The studies were undertaken in a range of population groups including those that are exposed to folate fortified foods, as well and non-fortified populations.
A meta-analysis review identified a correlation between tHcy and Alzheimer’s Disease, and suggested the effect was due to lower levels of vitamins B12, B6 and folate. These studies suggest a role for vitamin B12 in the prevention of cognitive decline. However, more long-term studies using biomarkers of vitamin B12 status and intervention studies from mid-life are needed to determine the effects of B vitamins on cognition.
Dietary factors associated with the development of osteoporosis include inadequate protein, calcium and vitamin D. More recently, there has been interest in the effect of other nutrients, including vitamin B12 on bone health.
Elevated tHcy has been associated with an increased risk of bone fractures, however it is not clear whether this is related to tHcy per se, to the level of vitamins B12, B6 or folate which are required for its metabolism, or to other causes of elevated tHcy such as environmental factors or underlying disease. A recent systematic review found that there is evidence for the association between tHcy and increased fracture risk, but less conclusive evidence for tHcy and low bone mineral density (BMD) or for the association between vitamin B12 and either fracture risk or low BMD.
Positive effects of the supplementation of B vitamins on BMD have been found in a subgroup of osteoporotic patients with high tHcy and stroke patients at risk for osteoporosis, but none in a group of healthy older people or from the secondary analysis of the HOPE Trial for CVD reduction.