Calorie Restriction with Optimum Nutrition
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CRON-WEB's Definitive Guide to Supplementation
"Well, it Can't Hurt, and it Might Help" Mistake

Go To >> Introduction • "Well, it Can’t Hurt, and it Might Help" Mistake • Tier I • Tier II • Tier III • References • Condensed ("Quick-Start") Guide

Vitamin A (Retinol/Retinyl Esters)

  • Higher Intake[34],[35] or Serum Levels[36] Increase Fracture risk
    • ”For every 1 mg [3330 IU] increase in daily intake of retinol, risk for hip fracture increased by 68% ... For intake > 1.5 mg [5000 IU] /d compared with < 0.5 mg [1665 IU]/d, … risk for hip fracture was doubled”. 34
    • Nurses’ Health Study: “women in the highest quintile of total vitamin A intake … had a significantly elevated relative risk (RR) of hip fracture compared with women in the lowest quintile of intake … attributable primarily to retinol (RR, 1.89 … comparing >/=2000 mcg [6660 IU]/d vs <500 mcg [1665 IU]/d). 35
  • Negative association of retinol intake with BMD; 34,[37],[38],[39] no association for serum levels in NHANES III.[40]
  • In animal studies,[41],[42] vitamin D does not fully counteract; most of the excess retinol in the first study 34 was from cod liver oil supplements taken for vitamin D in Nordic countries!
  • No risk from dietary carotenoids. 34, 35

Excess Zn or Zn:Cu

  • Competition for ligands (for absorption and utilization)
  • Frank Zn-induced Cu deficiency demonstrated in humans:
    • Zn:Cu of 23.5 (24 subjects) led to low CuZnSOD, high TC and LDL, low HDL, reduction in enkephalins, cardiac abnormalities (heart block, tachycardia, MI) (reviewed in ([43])).
    • Zn:Cu of 16 (one subject) led to decreases in ceruloplasmin, increased TC and LDL, arrhythmia. (reviewed in (43))
    • 50 mg Zn/day depresses CuZnSOD 20%.[44]
  • Other Cu-deficiency sequelae likely: impaired bone metabolism, poor glucose control, increased AGE, etc.

Excess Mn

  • Welders, other industrial inhalation exposure associated with manganism (Parkinsonian syndrome); reproduced in high-dose animal feeding studies; ecological study showed increased frequency of neurological symptoms in community with ~3.6-4.6 mg Mn/day from water as vs. 0.0072-0.03 and 0.16-0.5 mg/day.[45]
  • New case-control study links highest quartile [DEFINE THIS] Mn intake with 1.7-fold increase in PD risk.[46]
  • Vegetables, tea rich sources; vegetarian diets may contain 13-20 mg.
  • LOAEL from diet 15 mg (increases in serum Mn (‘should’ be tightly regulated)); UL 11 mg from all sources.[47]

Unbalanced alpha-tocopherol?

  • Alpha-tocopherol depletes gamma-tocopherol levels below baseline levels at 100 IU [48] (& perhaps 31 IU![49]). After 1 y alpha-tocopherol supplementation (1200 IU), tissue gamma-tocopherol levels take 2y to recover. [50] 30% depletion by 371 mg alpha-, even when balanced by >400 mg “other” tocopherols. [51] Alpha-tocopherol blocks tocotrienol action on HMG-CoA reductase if >30% of supplement.[52],[53], [54]
  • Little evidence of adverse outcomes (no increased risk of MI etc among supplement users; NS trend to dose-dependent increased risk of prostate cancer progressing 100 IU-400 IU[55]).

Synthetic beta-carotene? Read on...

Should we supplement? What, and how much? Read on...

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