Title: The clinical effects of severe and marginal zinc deficiency in humans
Key words: zinc, deficiency, acrodermatitis, enteropathica, metalloenzymes, zinc depletion, skin, hair, lymphoid tissue, parasitism, hypogonadism, growth, immune system, children, premenopausal, thymus, thymulin, AIDS, testosterone, Alzheimer’s disease
Date: Oct 2006
Author: Morgan, G
The clinical effects of severe and marginal zinc deficiency in humans
Zinc deficiency, though recognised for years in animals, was not recognised in humans until field studies were carried out amongst deprived groups in Iran and Egypt in the early 1960’s (Prasad 1961). Subsequently, with the description of acrodermatitis enteropathica (Barnes & Moynahan 1973), an inherited disorder of zinc absorption, and the effects of zinc-depleted IV nutrition regimes (Kay 1975), the specificity of the syndrome described by Prasad has been confirmed.
Zinc is the most abundant intracellular trace element and is a component in over 300 metalloenzymes playing key roles in cell membrane stability, cell replication, immunity and antioxidant activities, amongst other functions. In addition they play an important role in determining the tertiary structure of proteins such as transcription factors which help to modulate the activity of operons on the genome (Rhodes & Klug 1993). The involvement of this large group of enzymes helps to explain the close association zinc has with enzyme activity and growth within the cell. Cells and tissues with a rapid turnover rate, such as skin, hair, lymphoid tissue and the gastrointestinal mucosa, appear to be most sensitive to zinc deficiency, leading undoubtedly to many of the features of clinical zinc deficiency.
As described in the work of Prasad (Prasad 1961), the syndrome of zinc deficiency is characterised by dwarfism, hypogonadism, hepatosplenomegaly, dermatitis, an associated iron deficiency anaemia and immune impairment leading to parasitism and early death from bacterial and viral infections (Prasad 2001). Low animal protein and high phytate consumption appear to lead to a marked reduction in bioavailable zinc and the clinical features.
In developing countries plasma zinc estimations serve as a useful index of zinc status and, according to estimations (Prasad 2000) ranks zinc deficiency as of equal severity to iron deficiency worldwide. In developed countries with a higher standard of nutrition, leucocyte zinc content has been held to be a more sensitive marker of borderline zinc deficiency (Shenkin 1992, Prasad 1998) and, using this parameter, groups such as children less than 3 years old, adolescent girls, pregnant women, premenopausal women and the elderly have been shown to be at greatest risk. Combinations of increased demands and poor nutrition lead to this deficiency. The major effects are on growth and the immune system.
Growth effects of mild zinc deficiency have been most closely studied in utero and in young children. Effects have been most closely correlated with diminished levels of the insulin-like growth factor (Ninh 1996). In the most carefully controlled trial (Goldenberg 1995), significant differences in foetal birth weight differences in birthweight were related to both maternal size and plasma zinc levels. In children the effect of mild zinc deficiency has been more difficult to quantify although in one study in pre-school children in Santiago, Chile (Ruz 1997), where dietary intake was 66% of the RDA, zinc supplementation produced significant growth increments, though only in boys. Further supplementation studies are called for in young children and adolescent girls on vegetarian or fad diets.
Prospective studies have shown that zinc depletion produced by intakes of around 5mg/day lead to reduced thymulin production and shrinkage of the thymus gland and lymphoid tissue (Prasad 2000). Associated with this is a reduction in both the B and T lymphocyte population, a selective reduction Th1 and NK cells with an imbalance in the Th1/Th2 ratio and a significant compromise to the immune system. The role of zinc in, for example, AIDS requires further research.
Other areas of research are the effects of mild zinc deficiency on the function of oestrogen and androgen receptors (see Prasad 1998 for review). Surveys have shown that two thirds of premenopausal women may be deficient (NHANES II 1986) : this may well impact on hormonal function around the menopause. Testosterone levels and fertility are also likely to be affected in males. Further work also needs to look at the effect of zinc deficiency on cognition to follow up studies such as Penland’s study on Chinese children (Penland 1985) and Alzheimer’s disease (see Prasad 1998 for review).
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