Vitamin A (Retinol/Retinyl Esters)
- Higher Intake,
or Serum Levels
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,,,
no association for serum levels in NHANES III.
- In animal studies,,
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 ()).
- 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%.
- Other Cu-deficiency sequelae likely: impaired bone
metabolism, poor glucose control, increased AGE, etc.
- 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
- New case-control study links highest quartile [DEFINE THIS] Mn intake
with 1.7-fold increase in PD risk.
- 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.
- Alpha-tocopherol depletes gamma-tocopherol levels below baseline levels
at 100 IU  (& perhaps 31 IU!).
After 1 y alpha-tocopherol supplementation (1200 IU), tissue gamma-tocopherol
levels take 2y to recover. 
30% depletion by 371 mg alpha-, even when balanced by >400 mg “other”
 Alpha-tocopherol blocks tocotrienol action on HMG-CoA reductase
if >30% of supplement.,,
- 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).
Synthetic beta-carotene? Read on...
Should we supplement? What, and how much? Read